Polimorfisme Endoglin

Polymorfism endoglin.
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Reference Type: Journal Article

Record Number: 17
Polymorphisms in MMP-2 and MMP-9 promoter

regions are associated with endometriosis
Year: 2010
Author: M. Saare, M. Lamp, T. Kaart, H. Karro, U. Kadastik, A. Metspalu, M. Peters

and A. Salumets
Journal: Fertil Steril

Volume: 94
Issue: 4
Pages: 1560-3
In this case-control study, we investigated the potential associations of MMP-2 and

MMP-9 gene promoter region polymorphisms as well as MMP-2 promoter haplotypes
with susceptibility to endometriosis in women of caucasian origin. The results
demonstrated that polymorphisms in MMP-2 (-735 C/T) and MMP-9 (-1562 C/T) were
associated with elevated risk of endometriosis and that certain MMP-2 promoter
haplotypes were more common in control group.

Record Number: 12
Progesterone receptor gene polymorphisms and risk

of endometriosis: results from an international
collaborative effort
Year: 2010
Author: A. M. Near, A. H. Wu, C. Templeman, D. J. Van Den Berg, J. A. Doherty, M.

A. Rossing, E. L. Goode, J. M. Cunningham, R. A. Vierkant, B. L. Fridley, G.
Chenevix-Trench, P. M. Webb, S. K. Kjaer, E. Hogdall, S. A. Gayther, S. J. Ramus, U.
Menon, A. Gentry-Maharaj, J. M. Schildkraut, P. G. Moorman, R. T. Palmieri, R. B.
Ness, K. Moysich, D. W. Cramer, K. L. Terry, A. F. Vitonis, M. C. Pike, A. Berchuck and
C. L. Pearce

Polymorfism endoglin.enl Page 2
OBJECTIVE: To investigate the association between self-reported endometriosis and

the putative functional promoter +331C/T single nucleotide polymorphism and the
PROGINS allele. DESIGN: Control subjects from ovarian cancer case-control studies
participating in the international Ovarian Cancer Association Consortium. The majority
of controls are drawn from population-based studies. SETTING: An international
ovarian cancer consortium including studies from Australia, Europe, and the United
States. PATIENT(S): Five thousand eight hundred twelve white female controls, of
whom 348 had endometriosis, from eight ovarian cancer case-control studies.
INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genotypes for the +331C
T single nucleotide polymorphism and PROGINS allele and a history of endometriosis.
RESULT(S): The occurrence of endometriosis was reduced in women carrying one or
more copies of the +331 T allele (odds ratio = 0.65; 95% confidence interval:
0.43-0.98), whereas there was no association between the PROGINS allele and
endometriosis (odds ratio = 0.94, 95% confidence interval 0.76-1.16).
CONCLUSION(S): Additional studies of the +331C/T variant are warranted given the
current finding and the equivocal results of previous studies. The +331 T allele has
been shown to result in a reduced progesterone (P) receptor A to P receptor B ratio,
and if the observed association with endometriosis is confirmed it would suggest that
this ratio is important for this disease.

Record Number: 6
The genetics of sporadic ruptured and unruptured

intracranial aneurysms: a genetic meta-analysis of 8
genes and 13 polymorphisms in approximately 20,000
individuals
Year: 2010
Author: P. McColgan, K. Z. Thant and P. Sharma
Journal: J Neurosurg
Volume: 112
Issue: 4
Pages: 714-21
OBJECT: Intracranial aneurysms (IAs) are thought to have a multifactorial origin. The
authors undertook a comprehensive meta-analysis on all genes investigated using a
case-control model in ruptured (subarachnoid hemorrhage) and unruptured aneurysms.
METHODS: Electronic databases were searched until and including July 2008 for any
candidate gene studied in IA or subarachnoid hemorrhage using a case-control model.
The ORs and 95% CIs were determined for each gene-disease association using fixed
and random effect models. RESULTS: Thirty studies of 8 genes and 13 polymorphisms
were analyzed among 19,961 individuals (6622 cases and 13,339 controls). Two genes
and 3 polymorphisms were associated with IA. The eNOS gene T786C polymorphism
(OR 1.24, 95% CI 1.0-1.54; p = 0.05) and IL-6 gene G572C polymorphism (OR 7.08,
95% CI 2.85-17.57; p < 0.0001) both showed a significant association with ruptured
unruptured IA. The IL-6/G174C polymorphism exerted a significant protective effect
against IA (OR 0.49, 95% CI 0.25-0.95; p = 0.04). The other candidate genes
investigated (ACE, endoglin, APOE, elastin, MMP-3, and SERPINA3) showed no
significant associations. CONCLUSIONS: There is a likely genetic basis to sporadic
IAs. However, the evidence base is small when compared against other complex
disorders.

Record Number: 1
The genetics of sporadic ruptured and unruptured

intracranial aneurysms: a genetic meta-analysis of 8
genes and 13 polymorphisms in approximately 20,000
individuals
Year: 2010
Author: P. McColgan, K. Z. Thant and P. Sharma
Journal: J Neurosurg
Volume: 112
Issue: 4
Pages: 714-21
OBJECT: Intracranial aneurysms (IAs) are thought to have a multifactorial origin. The
authors undertook a comprehensive meta-analysis on all genes investigated using a
case-control model in ruptured (subarachnoid hemorrhage) and unruptured aneurysms.
METHODS: Electronic databases were searched until and including July 2008 for any
candidate gene studied in IA or subarachnoid hemorrhage using a case-control model.
The ORs and 95% CIs were determined for each gene-disease association using fixed
and random effect models. RESULTS: Thirty studies of 8 genes and 13 polymorphisms
were analyzed among 19,961 individuals (6622 cases and 13,339 controls). Two genes
and 3 polymorphisms were associated with IA. The eNOS gene T786C polymorphism
(OR 1.24, 95% CI 1.0-1.54; p = 0.05) and IL-6 gene G572C polymorphism (OR 7.08,
95% CI 2.85-17.57; p < 0.0001) both showed a significant association with ruptured
unruptured IA. The IL-6/G174C polymorphism exerted a significant protective effect
against IA (OR 0.49, 95% CI 0.25-0.95; p = 0.04). The other candidate genes
investigated (ACE, endoglin, APOE, elastin, MMP-3, and SERPINA3) showed no
significant associations. CONCLUSIONS: There is a likely genetic basis to sporadic
IAs. However, the evidence base is small when compared against other complex
disorders.

Record Number: 13
Polymorphisms in ESR1, ESR2 and HSD17B1 genes

are associated with fertility status in endometriosis
Year: 2010
Author: M. Lamp, M. Peters, E. Reinmaa, K. Haller-Kikkatalo, T. Kaart, U. Kadastik, H.

Karro, A. Metspalu and A. Salumets
Journal: Gynecol Endocrinol
Objective. To investigate whether polymorphisms in genes involved in biosynthesis and

signalling of sex steroids influence susceptibility to endometriosis and to infertility
associated with it. Materials and methods. Patients with endometriosis (n = 150) and
fertile controls (n = 199) were genotyped for polymorphisms in oestrogen receptor
genes ESR1 (rs2234693 - T/C single nucleotide polymorphism (SNP), dinucleotide
(TA)(n) repeat) and ESR2 (dinucleotide (CA)(n) repeat), progesterone receptor gene
PGR (rs10895068 - G/A SNP, 306-bp Alu-insertion), 17beta-hydroxysteroid
dehydrogenase type 1 gene HSD17B1 (rs605059 - A/G SNP), and aromatase gene
CYP19A1 (rs10046 - C/T SNP, (TTTA)(n) tetranucleotide repeat, 3-bp TCT insertion
deletion polymorphism). Results. The HSD17B1 A/G SNP A allele increased overall
endometriosis risk and the risk of stage I-II disease, while ESR1 longer (TA)(n) repeats
only correlated with susceptibility to stage I-II endometriosis. When considering
patients' fertility status, HSD17B1 A/G SNP A allele and ESR1 longer (TA)(n) repeats
were associated with endometriosis accompanied by infertility, while ESR2 shorter
(CA)(n) repeats were linked with endometriosis without infertility. Other polymorphisms
were distributed similarly among patients and controls. Conclusions. Genetic variants in
ESR1, ESR2, and HSD17B1 genes could modify susceptibility to endometriosis and
might influence the fertility status in endometriosis patients.

Record Number: 14
Association between genetic polymorphisms in

fibroblast growth factor (FGF)1 and FGF2 and risk of
endometriosis and adenomyosis in Chinese women
Year: 2010
Author: S. Kang, S. Z. Li, N. Wang, R. M. Zhou, T. Wang, D. J. Wang, X. F. Li, J. Bui

and Y. Li
Journal: Hum Reprod

Volume: 25
Issue: 7
Pages: 1806-11
BACKGROUND: Angiogenesis appears to be an important event in the

pathophysiology of endometriosis (EM) and adenomyosis. Two angiogenic factors,
fibroblast growth factor (FGF) 1 and 2, play a central role in the initiation of
angiogenesis. We investigated whether FGF1 -1385A/G and FGF2 754C/G
polymorphisms are associated with a risk of developing EM and adenomyosis.
METHODS: Genotypes were analyzed by the PCR-restriction fragment length
polymorphism method in two groups of women, of Han ethnicity in north China, aged
16-55 years: (1) 421 EM patients and 421 controls; (2) 269 adenomyosis patients and
269 controls. RESULTS: There was no difference in genotype distribution of the FGF1
-1385A/G polymorphism between adenomyosis cases and controls (P > 0.05), but the
frequency of the A allele in EM patients was lower than that in controls (P = 0.013).
Genotype and allele frequencies of the FGF2 754C/C polymorphism were significantly
different in both EM and adenomyosis cases versus control groups. Compared with C
C homozygotes, the G allele (C/G + G/G) was associated with a decreased
susceptibility to developing EM [odds ratio (OR) = 0.575, 95% confidence interval (CI) =
0.387-0.854] and adenomyosis (OR = 0.577, 95% CI = 0.367-0.906). Combined
genotype analysis of both polymorphisms also showed differences between cases
versus controls (all P < 0.001). CONCLUSIONS: Our study shows for the first time that
the FGF2 754C/G polymorphism may be associated with a risk of developing EM and
adenomyosis in north Chinese women. Carriers of the G allele in the FGF2 gene
appear to be protected from these gynecological diseases. Further studies in other
populations, and of other candidate genes, are now warranted.

Record Number: 15
Intercellular adhesion molecule-1 and interleukin-6

gene polymorphisms in patients with advanced-stage
endometriosis
Year: 2010
Author: S. J. Chae, G. H. Lee, Y. M. Choi, M. A. Hong, J. M. Kim, K. S. Lee, S. Y. Ku

and S. Y. Moon
Journal: Gynecol Obstet Invest

Volume: 70
Issue: 1
Pages: 34-9
BACKGROUND/AIMS: The aim of this study was to investigate the possibility that the
K469E and G241R polymorphisms in the intercellular adhesion molecule-1 (ICAM-1)
gene and the C-634G polymorphism in the interleukin (IL)-6 gene are associated with
endometriosis in the Korean population. METHODS: The ICAM-1 gene K469E and
G241R polymorphisms and the IL-6 gene C-634G polymorphism were evaluated in 390
patients with endometriosis and 351 controls by polymerase chain reaction-restriction
fragment length polymorphism analysis. RESULTS: The ICAM-1 gene G241R
polymorphism was not observed in all subjects. No differences were observed in the
ICAM-1 K469E and IL-6 C-634G genotype distributions and allele frequencies between
patients with endometriosis and controls. In subgroup analyses according to the stage
of endometriosis or bilaterality of ovarian endometriomas, no significant differences
were observed in the ICAM-1 gene K469E or the IL-6 gene C-634G polymorphism
frequencies between the subgroups and the controls. The combined analysis of the
ICAM-1 gene K469E polymorphism and the IL-6 gene C-634G polymorphism did not
show any additional significant findings. CONCLUSIONS: The K469E and G241R
polymorphisms in the ICAM-1 gene and the C-634G polymorphism in the IL-6 gene
may not be genetic factors related to susceptibility to advanced-stage endometriosis in
the Korean population.

Record Number: 16
CYP17 and CYP2C19 gene polymorphisms in patients

with endometriosis
Year: 2010
Author: G. Bozdag, A. Alp, Z. Saribas, S. Tuncer, T. Aksu and T. Gurgan
Journal: Reprod Biomed Online

Volume: 20
Issue: 2
Pages: 286-90
Endometriosis seems to be the result of a complex interaction between environmental

factors and various genes. In this regard, the cytochrome subfamily 17 (CYP17) may
play an important role by altering the biosynthesis of sex steroids. CYP2C19 is also an
important member of the cytochrome P450 (CYP) family, and related mutations may
result in an inability to fully metabolize environmental chemicals and cytokines, leading
to several diseases. This study sought to determine whether there is a relationship
between endometriosis and CYP17 T>C, CYP2C19 *2 and CYP2C19 *3
polymorphisms. When samples from 46 patients with endometriosis and 39 healthy
controls were analysed, A2A2 type mutation of the CYP17 gene was observed to be
more frequent in patients with endometriosis (34.8 versus 7.7%, P = 0.003). No
association was found between the severity of endometriosis and CYP2C19 *2 or
CYP2C19 *3 polymorphisms of the CYP2C19 gene. These results suggest that
mutations related with sex steroid metabolism seem to have an important role in
endometriosis. However, the relation between detoxification ability and endometriosis
should be examined in further studies with larger sample sizes.

Record Number: 11
Functional association of interleukin-18 gene -607 C/A

promoter polymorphisms with endometriosis
Year: 2010
Author: L. Ayaz, S. K. Celik, F. Cayan, N. Aras-Ates and L. Tamer
This study evaluated for the first time the relationship between interleukin-18 (IL-18)
C607A genotypes and endometriosis in 135 women with endometriosis and 84
controls. In the study population, IL-18 -607 *A homozygote and A allele were positively
correlated with the risk of developing endometriosis or the stage of endometriosis.

Record Number: 26
Association of estrogen receptor alpha and

interleukin-10 gene polymorphisms with
endometriosis in a Chinese population
Year: 2009
Author: J. Xie, S. Wang, B. He, Y. Pan, Y. Li, Q. Zeng, H. Jiang and J. Chen

Volume: 92
Issue: 1
Pages: 54-60
OBJECTIVE: To determine whether polymorphisms of the estrogen receptor alpha

(ERalpha) and interleukin-10 (IL-10) genes are associated with endometriosis in a
Chinese population. DESIGN: Association study. SETTING: University hospital.
PATIENT(S): Chinese women diagnosed with endometriosis by laparotomy or
laparoscopy. INTERVENTION(S): Determination of polymorphisms of the ERalpha and
IL-10 genes was performed by polymerase chain reaction and restriction fragment
length polymorphism analysis in 214 affected women and 160 controls. MAIN
OUTCOME MEASURE(S): Frequency and distribution of PvuII and XbaI
polymorphisms of ERalpha and of BslI, SspI, and RsaI polymorphisms of IL-10.
RESULT(S): There was no significant difference between the endometriosis patients
and the control groups in the genotype frequency of ERalpha-PvuII and promoter of
IL-10 gene polymorphisms in the position of -1082. However, the frequency of
ERalpha-XbaI and -592 or -819C alleles of IL-10 in the endometriosis group was
significantly higher than that of controls, and further analysis showed that the X allele of
ERalpha-XbaI was associated with endometriosis. CONCLUSION(S): The X allele of
ERalpha-XbaI and the -592 or -819 C allele of IL-10 are associated with endometriosis.

Record Number: 24
CYP17 and CYP19 gene polymorphisms in women

affected with endometriosis
Year: 2009
Author: M. T. Vietri, M. Cioffi, M. Sessa, S. Simeone, P. Bontempo, E. Trabucco, M.

Ardovino, N. Colacurci, A. M. Molinari and L. Cobellis

Volume: 92
Issue: 5
Pages: 1532-5
OBJECTIVE: To investigate whether CYP17 T>C polymorphism and polymorphisms

C1558T and Val80 of CYP19 are related to endometriosis. DESIGN: Clinical study.
PATIENT(S): Women affected with endometriosis (n = 104) and control group (n = 86).
The diagnosis of endometriosis was confirmed by the histologic examination of the
endometriotic lesions. RESULT(S): In patients affected with endometriosis, we
observed that AA and CC genotypes were significantly represented in Val80 and
C1558T polymorphisms of CYP19. CONCLUSION(S): The molecular mechanisms that
underlie the development of endometriosis are unclear. Both environmental and
genetic factors are involved in the pathogenesis of the disease. The inheritable
susceptibility to endometriosis justifies the growing interest in identifying genes and/or
genetic polymorphisms that predispose women to an increased risk of developing
endometriosis. The identification of single-nucleotide polymorphism (SNP), probably
linked to endometriosis, could help to explain its pathogenesis.

Record Number: 25
Functional genetic polymorphisms and female

reproductive disorders: part II--endometriosis
Year: 2009
Author: C. B. Tempfer, M. Simoni, B. Destenaves and B. C. Fauser
Journal: Hum Reprod Update

Volume: 15
Issue: 1
Pages: 97-118
BACKGROUND: Endometriosis has a strong genetic component, and numerous

genetic studies have been reported. METHODS: We have systematically reviewed
these studies and included 114 in our final selection. RESULTS: We found no
consistent evidence linking endometriosis with specific polymorphisms in genes
encoding inflammatory mediators, proteins involved in sex steroid metabolism, vascular
function and tissue remodelling. Although a number of polymorphisms have been
associated with endometriosis in selected populations, the associations have not been
independently confirmed, either because only single studies were carried out on these
markers/genes or because other studies reported no association. The most solid
evidence linking specific polymorphisms to endometriosis came from studies
investigating glutathione-S-transferase, a phase II detoxification enzyme. Carriage of
the GSTT1 null deletion variant showed consistent association with endometriosis with
a 29% increased risk; however, it cannot be excluded that this result was due to
publication bias, and this association should be independently confirmed in large-scale,
well-designed case-control studies. CONCLUSIONS: The evidence of an association
between genetic polymorphisms and endometriosis is weak. Carriage of the GSTT1
null deletion may moderately increase the risk of this disease. We suggest that the
methodology of association studies should be improved in order to identify and validate
associations in endometriosis.

Record Number: 21
[Association of single nucleotide polymorphisms in

VEGF gene with the risk of endometriosis and
adenomyosis]
Year: 2009
Author: Q. Liu, Y. Li, J. Zhao, R. M. Zhou, N. Wang, D. L. Sun, Y. N. Duan and S. Kang
Journal: Zhonghua Yi Xue Yi Chuan Xue Za Zhi

Volume: 26
Issue: 2
Pages: 165-9
OBJECTIVE: To investigate the association of single nucleotide polymorphisms (SNPs)

in VEGF gene with the risk of endometriosis and adenomyosis. METHODS: Genotypes
were analyzed by polymerase chain reaction-restriction fragment length polymorphism
(PCR-RFLP) method in 344 endometriosis patients, 174 adenomyosis patients, 360
frequency-matched control women of endometriosis and 199 frequency-matched
control women of adenomyosis. RESULTS: No significant difference was found in allele
frequencies and genotype distributions of the -460C/T polymorphism between patients
(endometriosis and adenomyosis) and control women (all P value > 0.05). However,
there were significant differences in genotype and allele distributions of the VEGF
-1154G/A polymorphism between patients (endometriosis and adenomyosis) and
control women (all P value < 0.05). The genotype frequencies of the VEGF -1154 AA,
GA, and GG in endometriosis patients and control women were 1.7%, 28.8%, 69.5%
and 5.8%, 32.8%, 61.4%, respectively; and the A and G allele frequencies in the two
groups were 16.1%, 83.9% and 22.2%, 77.8%, respectively. The genotype frequencies
of the VEGF -1154 AA, GA, and GG in adenomyosis patients and control women were
2.9%, 23.6%, 73.6% and 7.0%, 34.2%, 58.8%, respectively; and the A and G allele
frequencies in the two groups were 14.7%, 85.3% and 24.1%, 75.9% respectively.
Compared with GA+ AA genotype, GG genotypes could significantly increase the risk
of endometriosis (OR:1.43,95%CI:1.05-1.96) and adenomyosis
(OR:1.95,95%CI:1.26-3.03). CONCLUSION: The VEGF -1154G/A polymorphism was
associated with susceptibility to endometriosis and adenomyosis, and the GG genotype
could significantly increase the risk of developing endometriosis and adenomyosis.
However, the VEGF -460C/T polymorphism was not associated with susceptibility to
endometriosis and adenomyosis in the population studied.

Record Number: 19
Association of polymorphisms -1154G/A and -2578C

A in the vascular endothelial growth factor gene with
decreased risk of endometriosis in Chinese women
Year: 2009
Author: Q. Liu, Y. Li, J. Zhao, D. L. Sun, Y. N. Duan, N. Wang, R. M. Zhou and S. Kang
Journal: Hum Reprod

Volume: 24
Issue: 10
Pages: 2660-6
BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in

the development of endometriosis. The aim of this study was to investigate the
association of polymorphisms in the VEGF gene with the susceptibility to
endometriosis. METHODS: This study comprised 344 North Chinese women with
endometriosis and 360 healthy women without endometriosis recruited as control.
Genotyping of the VEGF gene polymorphisms at -460C/T, -1154G/A, -2578C/A and
+936C/T were performed by PCR and restriction fragment length polymorphism
analysis. RESULTS: No significant difference was found in allele and genotype
distributions of the -460C/T, +936C/T polymorphisms between patients and controls.
However, the frequencies of -1154G/A, -2578C/A genotype and allele were significantly
different between the two groups (all P-value <0.013). The -2578A/A, -1154A/A
genotypes were found less frequently in patients with endometriosis compared with
controls. The haplotype distributions derived from three polymorphisms (-2578C/A,
-1154G/A, -460C/T) differed between the two groups (P = 0.000). CONCLUSIONS: The
VEGF-460/-1154/-2578 TGC, CAA, TAA and TAC haplotypes were associated with
endometriosis. The -1154A and -2578A alleles may be protective against the
development of endometriosis in North Chinese women.

Record Number: 18
[Relationship between IL-10 promoter gene

polymorphisms and the susceptibility to
endometriosis]
Year: 2009
Author: P. He, X. M. Zhang, L. Deng and J. Y. Ma
Journal: Yi Chuan
Volume: 31
Issue: 5
Pages: 479-84
The purpose of this study was to investigate the relationship between IL-10 promoter
gene polymorphism and the susceptibility to endometriosis (EMs) in Chinese
population. Amplification refractory mutation system polymerase chain reactions
(ARMS-PCR) and DNA sequencing were performed to detect polymorphism of -1082G
A site and PCR-RFLP was used to determine the genotypes in -819T/C and -592A/C
sites. One hundred and nineteen Chinese women with different stage EMs and 120
controls were employed in this study. Although there were no significant differences in
the polymorphism of -1082 site between two groups (P>0.05), the frequencies of
-819C, -592C alleles and -819 CC+TC, -592 CC+AC genotypes were significantly
increased in EMs patients compared with the controls (P<0.05). The frequencies of
-819C, -592C alleles and -819 CC+TC, -592 CC+AC genotypes were significantly
increased in III-IV EMs patients compared with I-IIMs or controls (P<0.01). This
suggests that polymorphisms of IL-10-819 (T/C) and -592 (A/C) may be associated with
the susceptibility to EMs in Chinese population.

Record Number: 23
Vascular endothelial growth factor polymorphisms

(-460C/T, +405G/C, and 936C/T) and endometriosis:
their influence on vascular endothelial growth factor

expression
Year: 2009
Author: R. Cosin, J. Gilabert-Estelles, L. A. Ramon, F. Espana, J. Gilabert, A. Romeu

and A. Estelles

Volume: 92
Issue: 4
Pages: 1214-20
OBJECTIVE: To analyze three functional vascular endothelial growth factor (VEGF)

polymorphisms (-460C/T, +405G/C, and 936C/T) in women with and without
endometriosis and their correlation with VEGF expression in endometrial tissue and
peritoneal fluid (PF). DESIGN: Case-control study. SETTING: University-based
hospital. PATIENT(S): One hundred eighty-six women with endometriosis and 180
controls without the disease. INTERVENTION(S): Endometrial biopsies were
performed by aspiration and PF samples were obtained at laparoscopy. MAIN
OUTCOME MEASURE(S): VEGF polymorphisms (-460C/T, +405G/C, and 936C/T)
were determined using a polymerase chain reaction (PCR)-restriction fragment length
polymorphism assay. Quantitative real-time reverse transcriptase (RT)-PCR assay was
used to quantify VEGF-A messenger RNA (mRNA) and VEGF-A antigen levels were
quantified by ELISA. RESULT(S): Patients with endometriosis showed a higher VEGF
936T allele frequency than controls. However, the distribution of genotypes and allele
frequencies in the other two VEGF (-460C/T, +405G/C) polymorphisms was similar in
the endometriosis and control groups. Endometrium and PF from women with
endometriosis showed an increase in VEGF levels, but no association was found
between the VEGF polymorphisms studied and VEGF expression in endometrial tissue
and PF. CONCLUSION(S): These findings suggest that the VEGF 936C/T
polymorphism may be associated with the risk of endometriosis in a Caucasian
population, but the increased VEGF levels observed in endometriosis do not appear to
be associated with this polymorphism.

Record Number: 20
Role of CYP2C19 polymorphisms in patients with

endometriosis
Year: 2009
Author: F. Cayan, L. Ayaz, M. Aban, S. Dilek and L. T. Gumus

Volume: 25
Issue: 8
Pages: 530-5
AIM: To investigate the association of CYP2C19 genotypes with endometriosis.

METHODS: The study included 100 women who underwent laparotomy or
laparoscopy: 50 patients with endometriosis diagnosed with surgery and
histopathology, and 50 control subjects who had no evidence of endometriosis during
exploratory laparotomy or laparoscopy. Genomic DNA of subjects was extracted from
the whole blood using High Pure PCR template preparation kit. Genotyping of
CYP2C19 polymorphisms were detected by using a LightCycler CYP2C19 mutation
detection kit in a real-time PCR, and were compared between the two groups.
RESULTS: Logistic regression analyses showed that the CYP2C19*2 heterozygote
genotype was associated with a significantly increased risk of endometriosis. The odds
ratio of endometriosis for the CYP2C19*2 heterozygote genotype was 3.165 (p =
0.023) compared with the control group. CYP2C19*3 genotype was detected as wild in
all subjects in the endometriosis and control groups. CONCLUSION: Our results
suggest that CYP2C19*2 heterozygote genotype has higher risk of developing
endometriosis. Therefore, CYP2C19*2 allele gene polymorphisms may be associated
with genetic susceptibility of endometriosis.

Record Number: 27
Polymorphisms in the vascular endothelial growth

factor gene and the risk of familial endometriosis
Year: 2008
Author: Z. Z. Zhao, D. R. Nyholt, S. Thomas, S. A. Treloar and G. W. Montgomery
Journal: Mol Hum Reprod

Volume: 14
Issue: 9
Pages: 531-8
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic

protein suspected to be involved in the pathogenesis of endometriosis by establishing a
new blood supply to the human exfoliated endometrium. Several transcription
factor-binding sites are found in the VEGF 5'-untranslated region and variation within
the region increases the transcriptional activity. Six previous studies which tested
between one and three single nucleotide polymorphisms (SNPs) in samples comprising
105-215 cases and 100-219 controls have produced conflicting evidence for
association between the SNPs in the VEGF region and endometriosis. To further
investigate the reported association between VEGF variants and endometriosis, we
tested the four VEGF polymorphisms (-2578 A/C, rs699947; -460 T/C, rs833061; +405
G/C, rs2010963 and +936 C/T, rs3025039) in a large Australian sample of 958 familial
endometriosis cases and 959 controls. We also conducted a literature-based review of
all relevant association studies of these VEGF SNPs in endometriosis and performed a
meta-analysis. There was no evidence for association between endometriosis and the
VEGF polymorphisms genotyped in our study. Combined association results from a
meta-analysis did not provide any evidence for either genotypic or allelic association
with endometriosis. Our detailed review and meta-analysis of the VEGF polymorphisms
suggests that genotyping assay problems may underlie the previously reported
associations between VEGF variants and endometriosis.

Record Number: 7
[Association of endoglin gene polymorphisms with

cerebral stroke: a multiple center study of 1414 cases]
Year: 2008
Author: J. Shi, W. L. Zhang, H. Y. Zhang, A. Q. Ma, Y. H. Liao, D. W. Wang and R. T.

Hui
Journal: Zhonghua Yi Xue Za Zhi

Volume: 88
Issue: 29
Pages: 2049-52
OBJECTIVE: To investigate the association of 5'TCCCCC3' insertion polymorphism in

intron7 and the C1096G allele gene with the risk of cerebral stroke in Chinese
population. METHODS: Peripheral blood samples were collected from 1414 Chinese
patients with cerebral hemorrhage (n = 376), infarction (n = 629) or lacunar infarction (n
= 409) selected from 7 clinical centers in China and 1376 controls Single nucleotide
polymorphism (SNP) at the position 1096 was genotyped with polymerase chain
reaction (PCR) and restriction fragment length polymorphism assay. PCR and
polyacrylamide gel electrophoresis were used to examine the insertion/deletion
polymorphism in 187 cases of cerebral stroke and 190 controls. RESULTS: The
frequency of allele G at nucleotide 1096 of the cerebral stroke patients was 13.5%, not
significantly different from that of the controls (13.3%, chi(2) = 0.827, P = 0.352). There
were not significant differences in the distribution of GG and GC genotypes among the
patients with cerebral hemorrhage, infarction, and lacunar infarction respectively and
the controls. In the 187 cases and 190 controls, only 2 cases of heterozygote of the
insertion sequence were found with a frequency of 0.003. CONCLUSION: The SNP at
the position 1096 of the Endoglin gene and insertion/deletion polymorphism in
5'TCCCCC3' of intron 7 are not the risk factors of cerebral stroke in Chinese population.

Record Number: 2
[Association of endoglin gene polymorphisms with

cerebral stroke: a multiple center study of 1414 cases]
Year: 2008
Author: J. Shi, W. L. Zhang, H. Y. Zhang, A. Q. Ma, Y. H. Liao, D. W. Wang and R. T.

Hui
Journal: Zhonghua Yi Xue Za Zhi

Volume: 88
Issue: 29
Pages: 2049-52
OBJECTIVE: To investigate the association of 5'TCCCCC3' insertion polymorphism in

intron7 and the C1096G allele gene with the risk of cerebral stroke in Chinese
population. METHODS: Peripheral blood samples were collected from 1414 Chinese
patients with cerebral hemorrhage (n = 376), infarction (n = 629) or lacunar infarction (n
= 409) selected from 7 clinical centers in China and 1376 controls Single nucleotide
polymorphism (SNP) at the position 1096 was genotyped with polymerase chain
reaction (PCR) and restriction fragment length polymorphism assay. PCR and
polyacrylamide gel electrophoresis were used to examine the insertion/deletion
polymorphism in 187 cases of cerebral stroke and 190 controls. RESULTS: The
frequency of allele G at nucleotide 1096 of the cerebral stroke patients was 13.5%, not
significantly different from that of the controls (13.3%, chi(2) = 0.827, P = 0.352). There
were not significant differences in the distribution of GG and GC genotypes among the
patients with cerebral hemorrhage, infarction, and lacunar infarction respectively and
the controls. In the 187 cases and 190 controls, only 2 cases of heterozygote of the
insertion sequence were found with a frequency of 0.003. CONCLUSION: The SNP at
the position 1096 of the Endoglin gene and insertion/deletion polymorphism in
5'TCCCCC3' of intron 7 are not the risk factors of cerebral stroke in Chinese population.

Record Number: 30
Intron 1 and exon 1 alpha estrogen receptor gene

polymorphisms in women with endometriosis
Year: 2008
Author: H. Sato, N. C. Nogueira-de-Souza, P. D'Amora, I. D. Silva, M. J. Girao and E.

Schor

Volume: 90
Issue: 6
Pages: 2086-90
OBJECTIVE: To evaluate the association of intron 1 and exon 1 polymorphisms in the

estrogen receptor alpha gene (ER-alpha) with endometriosis in women. DESIGN:
Association study. SETTING: Endometriosis Unit, Federal University of Sao Paulo.
PATIENT(S): The control group consisted of volunteers older than 45 years who had
no evidence of endometriosis antecedents. Two groups with the disease were
evaluated: the first group had stage I or II endometriosis and the second group stage III
or IV. INTERVENTION(S): Polymerase chain reaction (PCR) followed by digestion with
HaeIII and MspI endonucleases (RFLP) were applied to detect intron 1 and exon 1
polymorphisms, respectively, in a total of 125 controls and 105 affected women. MAIN
OUTCOME MEASURE(S): Frequency and distribution of HaeIII and MspI
polymorphisms in ER-alpha. RESULT(S): No significant differences in the frequency of
polymorphisms either in intron 1 or exon 1 of ER-alpha were found when endometriosis
patients were compared with control subjects. Furthermore, the frequency of ER-alpha
polymorphisms within the two different groups of patients with disease was statistically
similar. The odds ratio between presence of intron 1 single-nucleotide polymorphisms
(SNP) and endometriosis was 0.904, and the odds ratio between exon 1 SNP and
endometriosis was 0.976. CONCLUSION(S): The evaluated polymorphisms were not
associated with endometriosis.

Record Number: 29
Association of tumor necrosis factor-{alpha} gene

polymorphisms with advanced stage endometriosis
Year: 2008
Author: G. H. Lee, Y. M. Choi, S. H. Kim, M. A. Hong, S. T. Oh, Y. T. Lim and S. Y.

Moon
Journal: Hum Reprod

Volume: 23
Issue: 4
Pages: 977-81
BACKGROUND: This study was performed to investigate whether specific haplotypes

and several single nucleotide polymorphisms in the promoter region of the tumor
necrosis factor (TNF)-alpha gene are associated with the risk of advanced stage
endometriosis in a Korean population. METHODS: This study comprised women with
(n = 246) or without (n = 248) endometriosis. The TNF:g.[-1031T > C], TNF:g.[-863C >
A] and TNF:g.[-857C > T] polymorphism in the TNF-alpha gene were assessed by
PCR-restriction fragment length polymorphism analysis, which utilized digestion by
BbsI, HypCH4IV and HypCH4IV restriction enzymes, respectively. In silico haplotypes
were deduced by using the Haploview version 3.32. RESULTS: The genotype
distribution of TNF:g.[-1031T > C] was significantly different between total
endometriosis patients and the controls (T/T of 56.9 versus 60.1%, T/C of 35.4 versus
37.5% and C/C of 7.7 versus 2.4%, respectively, P = 0.027). This difference at the
TNF:g.[-1031T > C] tends to increase in Stage IV endometriosis (P = 0.01). However,
there was no difference in the TNF:g.[-863C > A] and TNF:g.[-857C > T] site between
the two groups. Even when the endometriosis cases were subdivided into American
Society for Reproductive Medicine Stages III and IV, genotype differences were not
found. The CC homozygote at TNF:g.-863 was more frequently found in the controls
than Non-CC group (P = 0.04; odds ratio = 0.67; 95% confidence interval = 0.45-0.98).
All haplotypes and diplotypes, deduced by in silico analysis, showed no association
with subgroups or controls. CONCLUSIONS: Our results suggest that the genotype
frequencies at the TNF:g.[-1031T > C] and the TNF:g.[-863C > A] sites may be
associated with advanced stage endometriosis in the Korean population.

Record Number: 40
Association between endometriosis and

polymorphisms in endostatin and vascular
endothelial growth factor and their serum levels in
Korean women
Year: 2008
Author: J. G. Kim, J. Y. Kim, B. C. Jee, C. S. Suh, S. H. Kim and Y. M. Choi

Volume: 89
Issue: 1
Pages: 243-5
The aim of present study was to evaluate the relationship between endometriosis and
polymorphisms in the endostatin and vascular endothelial growth factor (VEGF) genes,
and their levels in serum in a Korean population. Serum endostatin levels (but not
VEGF levels) were negatively correlated with the development of endometriosis,
specifically in early-stage endometriosis patients, compared with women without
endometriosis, but endometriosis was not associated with the endostatin G(4349)A and
VEGF C(936)T polymorphisms.

Record Number: 31
Association of polymorphisms of the MMP-2 and

TIMP-2 genes with the risk of endometriosis in North
Chinese women
Year: 2008
Author: S. Kang, X. W. Zhao, N. Wang, S. C. Chen, R. M. Zhou and Y. Li

Volume: 90
Issue: 5
Pages: 2023-9
We investigated whether three polymorphisms in the matrix metalloproteinase-2

(MMP-2; -1306C-->T and -735C-->T) and tissue inhibitor of metalloproteinase-2
(TIMP-2; -418G-->C) genes were related to the risk of endometriosis in
reproductive-aged women with and without endometriosis. Our results indicate that the
TIMP-2 -418C/C homozygote may be a protective factor against the development of
endometriosis in North Chinese women.

Record Number: 22
Tumor necrosis factor (TNF)-TNF receptor gene

polymorphisms and their serum levels in Korean
women with endometriosis
Year: 2008
Author: S. J. Chae, H. Kim, B. C. Jee, C. S. Suh, S. H. Kim and J. G. Kim
Journal: Am J Reprod Immunol

Volume: 60
Issue: 5
Pages: 432-9
PROBLEM: The aim of this study was to investigate the relationship between the
polymorphisms of the tumor necrosis factor-alpha (TNT-alpha) and TNF receptor
(TNFR) genes and serum levels of TNF-alpha and its soluble receptor (sTNFR) in
Korean women with endometriosis. METHOD OF STUDY: The TNF-alpha C(-857)T,
C(-863)A and T(-1031)C, and TNFR1 A(36)G. TNFR2 T(676)G, A(1663)G, T(1668)G
and C(1690)T polymorphisms, and serum levels of TNF-alpha, sTNFR1, and sTNFR2
were analyzed in women with (n = 105) and without endometriosis (n = 101).
RESULTS: Serum sTNFR1 and sTNFR2 levels were significantly higher in women with
endometriosis than in those without endometriosis, whereas no difference in serum
TNT-alpha level was noted. Single polymorphisms of TNT-alpha and TNFR genes were
not significantly different between the two groups. The frequencies of the TNF-alpha T
C/C haplotype allele and the TNFR2 G/G/T haplotype allele were significantly
decreased in women with endometriosis compared to women without endometriosis.
Women carrying at least one copy of the TNFR2 T/G/T and /or G/G/C haplotype allele
had an approximately two times higher risk of endometriosis than women without these
haplotype alleles. CONCLUSION: The haplotype alleles of the TNT-alpha and TNFR2
gene polymorphisms are genetic factors associated with endometriosis, and circulating
sTNFR rather than TNT-alpha, may be involved in the development of endometriosis in
Korean women.

Record Number: 28
Genetic polymorphisms of matrix metalloproteinase

12 and 13 genes are implicated in endometriosis
progression
Year: 2008
Author: B. Borghese, J. D. Chiche, D. Vernerey, C. Chenot, O. Mir, G. Bijaoui, C.

Bonaiti-Pellie and C. Chapron
Journal: Hum Reprod

Volume: 23
Issue: 5
Pages: 1207-13
BACKGROUND: Matrix metalloproteinases (MMPs) may contribute to endometriosis.

We tested whether eight functional polymorphisms of these genes could modify the risk
of endometriosis. METHODS: In this case-control study, 227 endometriosis and 241
controls were genotyped for MMP1 -1607 1G/2G, MMP2 -1575 G/A (MMP2.1), -1306 C
T (MMP2.2), MMP3 -1612 5A/6A, MMP7 -153 C/T (MMP7.1), -181 A/G (MMP7.2),
MMP12 -82 A/G and MMP13-77 A/G. Association between MMP genotypes and
superficial (SUP), deep infiltrating (DIE) and endometriomas (OMA) was tested for
each polymorphism separately, using unconditional logistic regression and then for
combined genotypes, using the combination test. RESULTS: When considering all
cases, MMP2 polymorphisms were found to be significant, mainly due to DIE (P =
0.023). A small difference between SUP and controls was found for MMP7.2 (P =
0.032) and MMP12 (P = 0.035), in the absence of correction for multiple testing. Using
the combination test, the best association when comparing SUP with controls was
obtained for MMP12-MMP13 (P = 0.004) for the combined genotype A/G-A/A (odds
ratio = 27.60, 95% confidence interval: 2.80-272.40). CONCLUSIONS: These data
show a potential role for MMP12 -82 A/G and MMP13 -77 A/G combined
polymorphisms in superficial endometriosis. As no association was found with deep
infiltrating endometriosis, this combination of polymorphisms might protect from a more
in-depth penetration of tissues.

Record Number: 42
Interleukin-10 gene promoter polymorphisms and

their protein production in peritoneal fluid in patients
with endometriosis
Year: 2007
Author: X. Zhang, P. Hei, L. Deng and J. Lin


Volume: 13
Issue: 2
Pages: 135-40
Although associations of interleukin-10 (IL-10) gene promoter polymorphisms and their

protein production with endometriosis risk have been reported, the correlations remain
controversial. The objective of this study was to determine IL-10 gene promoter
polymorphisms at -1082, -819 and -592 sites and their protein production in peritoneal
fluid (PF) in patients with and without endometriosis. IL-10 gene promoter
polymorphisms at -1082 site were detected by amplification refractory mutation system
(ARMS)-PCR and that at -819 and -592 sites was genotyped by restriction fragment
length polymorphism (RFLP)-PCR. Protein levels of IL-10 in PF were measured by
enzyme-linked immunosorbent assay (ELISA). There were no significant differences in
the genotype and allele frequencies of IL-10 gene promoter polymorphisms at position
-1082 between the endometriosis and the control groups. However, the frequency of
-819 or -592 C alleles was significantly increased in patients with endometriosis
compared with controls. The protein levels of IL-10 in PF were statistically higher in the
endometriosis group than in the control group. Moreover, the polymorphisms at -1082,
-819 and -592 sites were associated with protein levels of IL-10 in PF in the
endometriosis group while in the control group only the polymorphisms at position
-1082 correlated with protein levels. Increased frequency of -819 or -592 C allele and
increased protein production of IL-10 in PF in patients with endometriosis compared
with controls and correlations of polymorphisms at -819 and -592 sites with protein
levels of IL-10 in PF in patients with endometriosis may suggest that polymorphisms at
-819 and -592 sites and their protein production are associated with endometriosis risk.

Record Number: 41
Interaction between cytochrome P450 gene

polymorphisms and serum organochlorine TEQ levels
in the risk of endometriosis
Year: 2007
Author: M. Tsuchiya, H. Tsukino, M. Iwasaki, H. Sasaki, T. Tanaka, T. Katoh, D. G.

Patterson, Jr., W. Turner, L. Needham and S. Tsugane

Volume: 13
Issue: 6
Pages: 399-404
Exposure to dioxins and polychlorinated biphenyls (PCBs) has been suggested as a

possible etiologic factor for endometriosis, but the association remains highly
controversial. To assess whether cytochrome P450 (CYP) gene polymorphisms
modulate the effect of dioxins and/or PCBs in endometriosis risk, we conducted a
case-control study among infertile Japanese women. A total of 138 eligible women
aged 20-45 were diagnosed laparoscopically and classified into three subgroups:
control (no endometriosis), early endometriosis (stages I-II) and advanced
endometriosis (stages III-IV). Neither CYP1A1 Ile462Val and CYP1B1 Leu432Val
polymorphisms (genotypes with versus genotypes without the minor allele) nor serum
dioxin and PCB toxic equivalency (TEQ) levels (low versus high) were independently
associated with either early or advanced endometriosis risk. However, genotypes with
the CYP1A1 462Val allele showed a statistically significant reduced risk of advanced
endometriosis in combination with high serum dioxin TEQ levels (adjusted odds ratio =
0.13, 95% confidence interval: 0.02-0.76) (P for interaction = 0.08). Although no
association was found between serum PCB TEQ level and advanced endometriosis in
any stratum of CYP1B1 Leu432Val polymorphism, a statistically significant interaction
was found (P for interaction = 0.05). CYP1A1 and CYP1B1 polymorphisms may modify
the relation between environmental exposure to organochlorine and advanced
endometriosis risk.

Record Number: 36
Association of three single nucleotide

polymorphisms of the E-cadherin gene with
endometriosis in a Chinese population
Year: 2007
Author: K. Shan, M. Xiao-Wei, W. Na, Z. Xiu-Feng, W. Deng-Gui, G. Wei, Z.

Zheng-Mao and L. Yan
Journal: Reproduction
Volume: 134
Issue: 2
Pages: 373-8
Endometriosis, one of the most frequent diseases in gynecology, is a benign but

invasive and metastatic disease. The altered expression of E-cadherin may play an
important role in developing endometriosis. In this paper, we discuss the association of
three single nucleotide polymorphisms (SNPs) on the E-cadherin gene and risk of
endometriosis. We examined the genotype frequency of three polymorphisms in 152
endometriosis patients and 189 control women. There was a significant difference in
the frequency of the E-cadherin 3'-UTR C --> T genotypes between endometriosis and
controls (P = 0.01). The frequency of the C allele in patients (71.1%) was significantly
higher than in the controls (63.8%; P = 0.04). When compared with the T/T + T/C
genotypes, the C/C genotype had a significantly increased susceptibility to
endometriosis, with an adjusted odds ratio of 1.79 (95% confidence interval =
1.17-2.76). No significant difference was found between endometriosis and control
women on two polymorphisms (-160 C --> A, -347 G --> GA) at the gene promoter
region of E-cadherin. The -160 C --> A and -347 G --> GA polymorphisms displayed
linkage disequilibrium (D' = 0.999). The -160 A/-347 GA haplotype was only detected in
endometriosis patients (2%). These data show a relation between the E-cadherin
3'-UTR C --> T polymorphism, the -160 A/-347 GA haplotype of two promoter
polymorphisms and risk of endometriosis, suggesting a potential role in endometriosis
development, at least in North Chinese women.

Record Number: 38
Association between susceptibility to advanced stage

endometriosis and the genetic polymorphisms of aryl
hydrocarbon receptor repressor and
glutathione-S-transferase T1 genes
Year: 2007
Author: S. H. Kim, Y. M. Choi, G. H. Lee, M. A. Hong, K. S. Lee, B. S. Lee, J. G. Kim

and S. Y. Moon
Journal: Hum Reprod

Volume: 22
Issue: 7
Pages: 1866-70
BACKGROUND: This study was performed to determine whether genetic

polymorphisms of aryl hydrocarbon receptor repressor (AhRR),
glutathione-S-transferase M1 (GSTM1) and glutathione-S-transferase T1 (GSTT1) are
associated with susceptibility to advanced stage endometriosis in a Korean population.
METHODS: This study comprised 316 women with advanced stage endometriosis and
256 control women without endometriosis. Genotyping of the AhRR codon 185 was
performed by real-time polymerase chain reaction (PCR) analysis. GSTM1 and GSTT1
genotyping for gene deletions were carried out by multiplex PCR analysis. RESULTS:
G allele frequency at codon 185 of AhRR was increased in patients with endometriosis
(P=0.047), and there was a trend for an association of C/G+G/G genotypes with risk of
endometriosis (P=0.06). The proportion of null mutation at GSTT1 also tended to
increase (P=0.06) in patients with endometriosis, whereas there was no difference in
the genotype distribution of GSTM1 genes. Analyzing AhRR and GSTT1 together, we
found that patients with high-risk genotypes at both loci have increased risk of
endometriosis, compared with patients without high-risk genotypes (P=0.015).
CONCLUSIONS: These findings suggest that the AhRR codon 185 and GSTT1
polymorphisms are associated with the risk of advanced stage endometriosis.

Record Number: 33
Association study between epidermal growth factor

receptor and epidermal growth factor polymorphisms
and endometriosis in a Japanese population
Year: 2007
Author: M. Inagaki, S. Yoshida, S. Kennedy, N. Takemura, M. Deguchi, N. Ohara and

T. Maruo

Volume: 23
Issue: 8
Pages: 474-8
OBJECTIVE: We investigated a possible association between endometriosis and

polymorphisms in the genes encoding epidermal growth factor (EGF) receptor (EGFR)
and EGF in a Japanese population. METHODS: We compared the distribution of the
Egfr+2073 A/T and Egf+61 G/A polymorphisms by polymerase chain
reaction-restriction fragment length polymorphism analysis in 146 affected women and
181 controls. RESULTS: No significant differences in the frequency and genotype
distribution of the Egfr+2073 A/T and Egf+61 G/A polymorphisms were found between
endometriosis patients with all disease stages and controls. Stratification by disease
stage had no effect on the results. CONCLUSION: The Egfr+2073 A/T and Egf+61 G/A
polymorphisms are not associated with an increased risk of endometriosis in a
Japanese population.

Record Number: 35
Polymorphisms and haplotypes of the gene encoding

the estrogen-metabolizing CYP19 gene in Korean
women: no association with advanced-stage
endometriosis
Year: 2007
Author: S. E. Hur, S. Lee, J. Y. Lee, H. S. Moon, H. L. Kim and H. W. Chung
Journal: J Hum Genet

Volume: 52
Issue: 9
Pages: 703-11
A variety of factors affect the development of endometriosis, including hormonal status

and genetic factors. The growth of endometriosis is stimulated by local estrogen
production in conjunction with circulating estrogen. The CYP19 gene encodes a steroid
aromatase that catalyses the conversion of C-19 androgens to estrogens. This study
investigated whether polymorphisms of the CYP19 gene are associated with the risk of
advanced endometriosis in Korean women. Blood samples were collected from 224
female patients with endometriosis of stages III and IV, as diagnosed by both
pathologic and laparoscopic findings, and from a control group comprising of 188
women undergoing laparoscopic surgery or laparotomy for nonmalignant lesions.
Single-nucleotide polymorphisms, restriction fragment length polymorphisms, and
tetranucleotide tandem repeat polymorphisms were discriminated by the polymerase
chain reaction (PCR). Haplotype analysis was also performed. CYP19 115T>C,
240G>A, and 1531C>T polymorphisms and [TTTA]n tetranucleotide repeat
polymorphisms in the CYP19 gene and their haplotypes were not significantly
associated with the risk of endometriosis. The risk of endometriosis also did not
increase significantly with the number of higher risk alleles of the CYP19 gene. In
conclusion, our findings suggest that CYP19 genetic polymorphisms are not associated
with advanced-stage endometriosis in Korean women.

Record Number: 34
Endometriosis and genetic polymorphisms

Year: 2007
Author: H. Falconer, T. D'Hooghe and G. Fried
Journal: Obstet Gynecol Surv

Volume: 62
Issue: 9
Pages: 616-28
Endometriosis is a benign gynecological disease with an unclear pathophysiology

characterized by ectopic endometrium causing endometrium-like inflammatory lesions
outside the uterine cavity. Recently, a number of studies have investigated genetic
polymorphisms as a possible factor contributing to the development of endometriosis.
In this review, we have summarized current data regarding genes with nucleotide
polymorphisms investigated with regard to endometriosis. We searched PubMed for
publications on endometriosis and polymorphism and found 108 publications between
January 1979 and September 2005. These were classified according to the type of
genetic polymorphism investigated and whether the result favored or did not favor
association with endometriosis. We found a strikingly large amount of conflicting
results. About 50% of the reviewed studies demonstrated positive correlations between
different polymorphisms and endometriosis. This relation is most clearly seen in groups
1 (cytokines and inflammation), 2 (steroid-synthesizing enzymes and detoxifying
enzymes and receptors), 4 (estradiol metabolism), 5 (other enzymes and metabolic
systems), and 7 (adhesion molecules and matrix enzymes). Group 8 (apoptosis,
cellcycle regulation, and oncogenes) seemed to be negatively correlated with the
disease, whereas group 3 (hormone receptors), 6 (growth factor systems), and
especially 9 (human leukocyte antigen system components) showed a relatively strong
correlation. The review indicates that polymorphisms may have a limited value in
assessing possible development of endometriosis. TARGET AUDIENCE: Obstetricians
& Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this
article, the reader should be able to recall the complexity of attempting to link
endometriosis to single nucleotide polymorphisms (SNPs), explain that the literature is
varied on results and recommendations and is population specific, and state that there
are some SNP relationships that are clinically stronger than others.

Record Number: 39
Genetic polymorphisms of cytochrome P450cl7alpha

(CYP17) and progesterone receptor genes (PROGINS)
in the assessment of endometriosis risk
Year: 2007
Author: C. V. De Carvalho, N. C. Nogueira-De-Souza, A. M. Costa, E. C. Baracat, M.

J. Girao, P. D'Amora, E. Schor and I. D. da Silva

Volume: 23
Issue: 1
Pages: 29-33
We designed the present study in order to evaluate the eventual role of polymorphisms
in the genes encoding cytochrome P450c17alpha (CYP17) and the progesterone
receptor (PROGINS) as risk factors for endometriosis development. Eligible cases
consisted of 121 women with surgically confirmed endometriosis who underwent
treatment in a hospital in Sao Paulo, Brazil during the period from September 2003 to
September 2005. The 281 controls were participants with normal gynecological as well
as pelvic ultrasound evaluation, who did not have any gynecological conditions during
their reproductive lives such as pelvic pain and/or dyspareunia nor infertility history.
Genomic DNA was obtained from buccal cells and processed for DNA extraction using
the GFX DNA extraction kit (GE Healthcare). The CYP17 (-34T-->C) polymerase chain
reaction-restriction fragment length polymorphism assay has been described
previously, as has the progesterone receptor polymorphism (PROGINS) detection
assay. PROGINS heterozygosis genotype frequencies were shown to be statistically
higher in endometriosis cases compared with controls. On the other hand, differences
in the CYP17 polymorphism (-34T-->C) frequencies were not even close to significance
(p = 0.278) according to our findings.

Record Number: 37
Single nucleotide polymorphisms and haplotypes of

the genes encoding the CYP1B1 in Korean women:
no association with advanced endometriosis
Year: 2007
Author: Y. J. Cho, S. E. Hur, J. Y. Lee, I. O. Song, H. S. Moon, M. K. Koong and H. W.

Chung
Journal: J Assist Reprod Genet

Volume: 24
Issue: 7
Pages: 271-7
OBJECTIVE: To investigate whether single nucleotide polymorphisms and its

haplotypes of gene encoding CYP1B1 are associated with the risk of advanced
endometriosis in Korean women. METHODS: We investigated 221 patients with
histopathologically confirmed endometriosis rAFS stage III/IV and 188 control group
women who were surgically proven to have no endometriosis. The genetic distribution
of four different CYP1B1 polymorphisms at Ala119Ser, Leu432Val, Asp(449)(C>T),
Asn453Ser were analyzed by polymerase chain reaction (PCR) and restriction
fragment length polymorphism of PCR products. Haplotype analysis was also
performed. RESULTS: We found no overall association between each individual
CYP1B1 genotype or haplotype and the risk of endometriosis. Also, the odds ratio of
each haplotypes of CYP1B1 showed no association with the risk of endometriosis.
CONCLUSIONS: These results suggest that CYP1B1 genetic polymorphism may not
be associated with development of advanced endometriosis in Korean women.

Record Number: 32
Modulating interaction of glutathione-S-transferase

polymorphisms with smoking in endometriosis
Year: 2007
Author: M. Aban, D. Ertunc, E. C. Tok, L. Tamer, M. Arslan and S. Dilek
Journal: J Reprod Med

Volume: 52
Issue: 8
Pages: 715-21
OBJECTIVE: To evaluate the interaction of glutathione-S-transferase (GST) gene

polymorphisms and smoking as a risk factor for endometriosis. STUDY DESIGN: The
study group consisted of 150 women who were diagnosed by means of surgery and
histopathology as having endometriosis. The control group consisted of 150 women
who displayed no evidence of endometriosis during exploratory laparotomy or
laparoscopy. We assessed the interaction of smoking and GSTM1 and GSTT1
polymorphisms in these patients. RESULTS: Logistic regression analyses showed that
the GSTM1-null allele was associated with a significantly increased risk of
endometriosis and smoking with a decreased risk of endometriosis separately. There
was no association between endometriosis and the GSTT1-null allele. The interaction
of smoking and GST polymorphisms showed a joint effect. We found that the
GSTM1-null allele was more prevalent in active smoking endometriosis patients
(63.4%) than in the controls (35.0%), and the difference was statistically significant. A
similar tendency was also observed in the GSTT1 allele distribution. CONCLUSION:
Genetic factors could modify the response to environmental pollutants in endometriosis.

Record Number: 43
[Research on relationship between gene

polymorphisms of interleukin-1 family and
endometriosis]
Year: 2006
Author: J. Wen, L. Deng and X. M. Zhang
Journal: Zhejiang Da Xue Xue Bao Yi Xue Ban

Volume: 35
Issue: 6
Pages: 653-7
OBJECTIVE: To investigate whether interleukin-1 beta (IL-1beta ) and interleukin-1

receptor antagonist (IL-1RA) gene polymorphisms are associated with endometriosis
(EMs) in Chinese women. METHODS: One hundred and thirty-eight patients with EMs
and 100 women without EMs were enrolled in the study. Polymorphisms for IL-1
beta-511 promoter, IL-1 beta exon 5, and IL-1RA were detected by polymerase chain
reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULT: There
were no significant differences about the distribution of the genotypes and alleles of
IL-1 beta -511 promoter and IL-1 beta exon 5 in two groups (P > 0.05). The frequencies
of A1/A1, A1/A2, A1/A4 and A2/A2 of IL-1RA gene were 84.1 %, 12.3 %, 2.9 % and 0.7
% in EMs and 95 % , 4 % ,1 % and 0 % in controls, respectively (P=0.042). The A1, A2
and A4 alleles were 91.7 % , 6.9 % and 1.4 % in EMs and 97.5 % , 2 % and 0.5 % in
controls (P=0.019). In comparison with the reference genotype, the wild A1/A1
homozygote, the odds ratio for A1/A2 was 3.48 (95 % CI: 1.13 - 10.69). Compared with
the A1 allele, the odds ratio for the A2 allele was 3.66 (95 % CI: 1.23 - 10.94).
CONCLUSION: Association between the IL-1 beta-511 promoter,IL-1 beta exon 5
polymorphisms and EMs in China is not found. However, the A2 allele of IL-1RA gene
may be one of the risk factors for the Chinese women in Zhejiang Province to suffer
EMs.

Record Number: 51
Polymorphisms in the promoter regions of the matrix

metalloproteinases-7, -9 and the risk of endometriosis
and adenomyosis in China
Year: 2006
Author: K. Shan, Z. Lian-Fu, D. Hui, G. Wei, W. Na, J. Xia and L. Yan

Volume: 12
Issue: 1
Pages: 35-9
Matrix metalloproteinases (MMPs) may contribute to the development of endometriosis.

The aim of this study was to assess the effects of the polymorphisms in the promoters
of MMP-7 (181A/G) and MMP-9 (1562C/T) on the risk of occurrence of endometriosis
and adenomyosis. We genotyped 219 patients (143 women with endometriosis, 76
women with adenomyosis) and 160 control women in North China. There was a
significant difference in frequency of the MMP-7 genotype between endometriosis and
controls (P = 0.01) and also between adenomyosis and controls (P = 0.01). The
frequency of the G allele in two groups of patients (7.3 and 7.9%) was significantly
higher than in the controls (2.8%) (P = 0.01 and 0.01, respectively). Compared to the A
A genotype, the genotype with the -181G allele showed a significantly increased
susceptibility to both diseases, with adjusted odds ratio of 2.62 [95% confidence
interval (CI) = 1.17-5.87] for endometriosis and 3.14 (95% CI = 1.26-7.81) for
adenomyosis. However, the overall genotype and allelotype distribution of the MMP-9
in the two case groups were not different from that of controls. We conclude that
MMP-7-181A/G polymorphism has a potential to be a susceptibility factor for
endometriosis and adenomyosis while MMP-9-1562C/T polymorphism may not provide
a useful marker to predict susceptibility to endometriosis and adenomyosis, at least in
women from North China.

Record Number: 52
Evaluation of clinical parameters and estrogen

receptor alpha gene polymorphisms for patients with
endometriosis
Year: 2006
Author: S. P. Renner, R. Strick, P. Oppelt, P. A. Fasching, S. Engel, R. Baumann, M.

W. Beckmann and P. L. Strissel
Journal: Reproduction
Volume: 131
Issue: 1
Pages: 153-61
Endometriosis is a chronic inflammatory disease, which is especially found in women

with subfertility problems with an incidence of up to 30%. The disease is considered an
estrogen-dependent disorder, where DNA polymorphisms of the estrogen receptor
alpha (ERalpha) in connection with endometriosis are controversially discussed. From
a German population of women, clinical data associated with the disease, including the
American Fertility Society (AFS) I-IV classification, and non-clinical parameters were
evaluated statistically in endometriosis patients (n = 98) and in control women (n = 98)
without endometriosis. Using a multivariate statistical analysis, significant associations
of endometriosis with dysmenorrhea (P < 0.001) and allergies against medicaments (P
= 0.042) were found. A positive trend between first grade family history of
endometriosis and allergies against medicaments was also observed, suggesting a
genetic relationship. From both collectives, DNA from peripheral blood was analyzed
for the frequency of the ERalpha DNA polymorphisms Xba1 (A/G) and PvuII (T/C) in
intron 1 and the ERalpha exonic DNA polymorphism (G229A) with an amino acid
exchange (Gly77Ser) in the transactivation domain. DNA samples from endometriosis
lesions and control tissues from the same collectives were also analyzed for the exonic
G229A polymorphism. Only homozygote wild-type alleles for the polymorphism G229A
were found, making it a rare polymorphism in mid-European individuals. Allele types for
the PvuII and Xba1 polymorphisms were analyzed with the observed statistically
significant clinical parameters and showed no significant association with
endometriosis; however a trend with AFS IV was noted, which could contribute to
lesion severity. In conclusion, the analyzed polymorphisms in the ERalpha do not have
a functional role concerning specific clinical parameters associated with endometriosis.

Record Number: 50
Estrogen receptor gene polymorphisms are

associated with recurrence of endometriosis
Year: 2006
Author: S. Luisi, L. Galleri, F. Marini, G. Ambrosini, M. L. Brandi and F. Petraglia


Volume: 85
Issue: 3
Pages: 764-6
The presence of gene polymorphisms of the estrogen receptors ERalpha (PvuII and
XbaI) and ERbeta (AluI) in 61 women with endometriosis was investigated. A
statistically significant correlation between PvuII ERalpha gene polymorphism (PvuII),
both in homozygosity (PP) and in heterozygosity (Pp), and a recurrence of
endometriosis was found. In conclusion, women affected by endometriosis with the
ERalpha polymorphic allele, even if heterozygous, have a worse prognosis, and these
results suggest that the ERalpha gene polymorphisms may be included among the
genetic risk factors for endometriosis.

Record Number: 47
Association of two polymorphisms in the peroxisome

proliferator-activated receptor-gamma gene with
adenomyosis, endometriosis, and leiomyomata in
Japanese women
Year: 2006
Author: M. Kiyomizu, J. Kitawaki, H. Obayashi, M. Ohta, H. Koshiba, H. Ishihara and

H. Honjo
Journal: J Soc Gynecol Investig

Volume: 13
Issue: 5
Pages: 372-7
OBJECTIVE: The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is

a nuclear hormone receptor that plays an important role in many diseases. This study
investigated whether two polymorphisms (Pro12Ala in exon B and C161T in exon 6) of
the PPAR-gamma2 gene are related to adenomyosis, endometriosis, or leiomyomata.
METHODS: A total of 390 patients with adenomyosis, endometriosis, and/or
leiomyomata were classified into four groups: 103 patients with adenomyosis (21
adenomyosis only and 82 adenomyosis with endometriosis and/or leiomyomata), 95
patients with endometriosis only, 100 patients with leiomyomata only, and 92 patients
with endometriosis and leiomyomata. RESULTS: There was no association between
distribution of genotype or allele frequencies for the PPAR-gamma Pro12Ala
polymorphism and the presence of adenomyosis, endometriosis, and/or leiomyomata.

However, compared with results for controls, the PPAR-gamma 161CC genotype and
161C allele frequencies were significantly increased in patients with adenomyosis
(genotype: chi2 = 8.185, corrected P value [Pc] = .0169; allele: chi2 = 8.337, Pc =
.0155) and in patients with endometriosis (genotype: chi2 = 6.748, Pc = .0375; allele:
chi2 = 6.413, Pc = .0453). CONCLUSION: The results suggest that the PPAR-gamma
161CC genotype could be a genetic risk factor for adenomyosis and endometriosis,
whereas the Pro12Ala polymorphism was not associated with these
estrogen-dependent benign uterine diseases in a Japanese population.

Record Number: 44
Synergistic effect of interleukin-6 promoter (IL6 -634C

G) and intercellular adhesion molecule-1 (ICAM-1
469K/E) gene polymorphisms on the risk of
endometriosis in Japanese women
Year: 2006
Author: J. Kitawaki, M. Kiyomizu, H. Obayashi, M. Ohta, H. Ishihara, G. Hasegawa, N.

Nakamura, T. Yoshikawa and H. Honjo

Volume: 56
Issue: 4
Pages: 267-74
PROBLEM: Endometriosis is an immune-related, chronic inflammatory disease with a

polygenic predisposition. The aim of this study was to investigate whether the
interleukin-6 (IL-6) gene promoter region polymorphism (-634C/G) and the intercellular
adhesion molecule-1 (ICAM-1) gene 469K/E polymorphism are responsible in part for
the genetic susceptibility to endometriosis. METHODS OF STUDY: The IL-6 -634C/G
and ICAM-1 469K/E genotypes were determined in 202 patients with endometriosis
and 236 control women by polymerase chain reaction-restriction fragment length
polymorphism. RESULTS: There were no differences in the IL-6 -634C/G or the
ICAM-1 469K/E genotypes and allele frequencies between control women and
endometriosis patients collectively, or between control women and each clinical
subgroup of endometriosis patients. Interestingly, the frequency of ICAM-1 EE
homozygotes who concomitantly carried the IL-6 -634G allele was significantly higher
in patients with endometriosis (chi(2) = 6.458, P = 0.0396, d.f. = 2). CONCLUSION:
Our results suggest that the IL-6 -634C/G and ICAM-1 469K/E polymorphisms
synergistically affect the susceptibility for endometriosis in the Japanese population.

Record Number: 49
CYP17, CYP1A1 and COMT polymorphisms and the

risk of adenomyosis and endometriosis in Taiwanese
women
Year: 2006
Author: S. H. Juo, T. N. Wang, J. N. Lee, M. T. Wu, C. Y. Long and E. M. Tsai
Journal: Hum Reprod

Volume: 21
Issue: 6
Pages: 1498-502
BACKGROUND: The aim of the study was to test whether the COMT, CYP1A1 and
CYP17 genes influence the risk of developing adenomyosis and endometriosis.
METHODS: We conducted two case-control studies, where the cases (n = 198) had
either of the two diseases, and controls (n = 312) were disease-free women. For the
COMT gene, we selected the G/A nonsynonymous single-nucleotide polymorphism
(SNP) that leads to valine-to-methionine (Val/Met) substitution. For the CYP1A1 gene,
we used a functional T/C SNP in the 3'-noncoding region, and we genotyped a T/C
functional SNP in the 5' region of the CYP17 gene for the present study.
Hardy-Weinberg equilibrium was checked in both cases and controls. Logistic
regression models were used to evaluate the genetic effect, with adjustment for other
covariates. RESULTS: We found that the homozygous COMT genotype that encodes
low enzyme activity had an increased risk for adenomyosis with an age-adjusted odds
ratio of 3.2 (95% confidence interval 1.3-7.8; P = 0.006). The COMT gene, however,
was not associated with endometriosis. Neither the CYP1A1 nor CYP17 genes had any
significant association with either of the two diseases. CONCLUSION: The COMT gene
significantly influences the risk of adenomyosis but not endometriosis. The present
study does not provide evidence to support any of the three genes exerting pleiotropic
effects on both diseases.

Record Number: 46
P53 codon 11, 72, and 248 gene polymorphisms in

endometriosis
Year: 2006
Author: Y. Y. Hsieh and C. S. Lin
Journal: Int J Biol Sci

Volume: 2
Issue: 4
Pages: 188-93
OBJECTIVE: Mutated p53 gene is related to the instability of cell growth and cell cycle
progression. We aimed to evaluate the association between endometriosis and p53
codon 11, 72 and 248 gene polymorphisms. PATIENTS AND METHODS: Women were
divided into two groups: (1) moderate/severe endometriosis (n=148), and (2)
non-endometriosis groups (n=150). P53 gene polymorphisms include codon11 Glu/Gln
or Lys (GAG->CAG or AAG), codon 72 Arg/Pro (CGC->CCC), and codon 248 Arg/Thr
(CGG->TCG). These gene polymorphisms were amplified by polymerase chain
reaction and detected by electrophoresis after restriction enzyme (Taq I, BstU I, Hap II)
digestions. Associations between the endometriosis and p53 polymorphisms were
evaluated.RESULTS: The distributions of p53 codon 72 polymorphisms in both groups
were significantly different. The proportions of Arg homozygotes/heterozygotes/Pro
homozygotes in both groups were 9.5/66.2/24.3% and 30.7/50/19.3%. The proportions
of Arg/Pro alleles were 42.6/57.4% and 56/44%. The distributions of p53 codon 11 and
248 polymorphisms in both groups were non-significantly different. All individuals
appeared the wild genotypes (Glu11 and Arg248 homozygotes).CONCLUSION:
Association between endometriosis and p53 codon 72 polymorphism exists. P53 codon
72*Pro-related genotype and allele are related with higher susceptibility of
endometriosis. P53 codon 11 and 248 polymorphisms are not related with
endometriosis susceptibility.

Record Number: 56
Association of endometriosis risk and genetic

polymorphisms involving sex steroid biosynthesis
and their receptors: a meta-analysis
Year: 2006
Author: S. W. Guo
Journal: Gynecol Obstet Invest

Volume: 61
Issue: 2
Pages: 90-105
Endometriosis is a sex steroids-dependent disease. It has been postulated that certain

genetic polymorphisms involved in sex steroids biosynthesis and metabolisms may be
associated with increased risk of developing endometriosis. Despite a deluge of reports
of positive associations of endometriosis with numerous polymorphisms involving sex
steroids production and metabolism, the results are often conflicting. We performed a
meta-analysis of 12 association studies on 5 genes (CYP17, CYP19, AR, PR and ER).
We found that many reported positive findings were not supported by the data due to
faulty analysis. There have been no functional data that support a putative relationship
of these genetic polymorphisms with endometriosis. A handful of positive findings so far
have not been independently replicated, and should be viewed as preliminary. In
addition, these findings should be counterbalanced by legitimate concerns of multiple
comparisons, small prior probability of association with a particular polymorphism,
proper selection of controls, and lack of replication (at least until now). In future
association studies, it may be productive to put more thought to study design,
execution, and data analysis.

Record Number: 54
The association of endometriosis risk and genetic

polymorphisms involving dioxin detoxification
enzymes: a systematic review
Year: 2006
Author: S. W. Guo
Journal: Eur J Obstet Gynecol Reprod Biol

Volume: 124
Issue: 2
Pages: 134-43
Genetic polymorphisms involving genes encoding for dioxin detoxification enzymes

have been implicated as a risk factor for endometriosis, but individual studies have
been equivocal and controversial. We therefore performed a systematic review of 10

studies on association of endometriosis and various genes involved in dioxin
detoxification process excluding GSTM1/GSTT1. We found that almost all genetic
variants involving CYP1A1, CYP2E1, EPHX1, AHR, ARNT, AHRR, and NAT1 that
have been investigated by single studies show no association with endometriosis. Two
genetic variants were reported to be associated with endometriosis, with each variant
only investigated by a single study and there has been no independent confirmation so
far. For CYP1A1 MspI polymorphisms, women with +/- and +/+ genotype have about
40% of increased risk of endometriosis as compared with women of -/- genotype.
However, there is no strong indication that CYP1A1 MspI polymorphism is consistently
associated with endometriosis. For NAT2 polymorphisms, there is no evidence that it is
associated with endometriosis.

Record Number: 48
Analysis of two polymorphisms in the promoter

region of matrix metalloproteinase 1 and 3 genes in
women with endometriosis
Year: 2006
Author: M. M. Ferrari, M. L. Biondi, G. Rossi, B. Grijuela, S. Gaita, G. Perugino and P.

Vigano
Journal: Acta Obstet Gynecol Scand

Volume: 85
Issue: 2
Pages: 212-7
BACKGROUND: Matrix metalloproteinases are a family of proteolytic enzymes that can

degrade extracellular matrix components and have been implicated in connective tissue
remodeling associated with cancer invasion and metastasis. These proteins are also
involved in the invasive events underlying endometriotic lesion formation and
aggressive behavior. Given the established genetic background of endometriosis, the
aim of this study was to examine the potential impact of two polymorphisms in the gene
promoter region of two of these enzymes, matrix metalloproteinases 1 and 3, on
predisposition and severity of the disease. METHODS: Genomic DNA was obtained
from 56 Italian Caucasian women with a surgical diagnosis of endometriosis and a
control group of 71 age-matched Caucasian healthy female blood donors. In control
women, endometriosis was ruled out by evaluation of the medical history, gynecologic
examinations, and ultrasound scanning. Two polymorphisms have been specifically
investigated: 1. a single insertion polymorphism (2G) in the matrix metalloproteinase-1
promoter region known to elevate transcriptional level of matrix metalloproteinase-1;

and 2. a single insertion/deletion polymorphism (5A/6A) located in the promoter of the
matrix metalloproteinase-3 gene with functional significance in the regulation of its
expression. Genotypes were determined by PCR amplification and sequence analysis.
RESULTS: Allele and genotype frequencies of both polymorphisms did not significantly
differ between endometriosis and control groups. Moreover, no significant difference for
both polymorphisms was observed in relation to the clinical stage and recurrence
status of the disease. CONCLUSIONS: This is the first study that has evaluated the
possibility that gene variants of matrix metalloproteinases might be involved in the
susceptibility to endometriosis. However, these results suggest that matrix
metalloproteinases 1 and 3 promoter polymorphism do not constitute an important
factor for the genetic predisposition to endometriosis and its invasive behavior in the
Italian population.

Record Number: 45
Polymorphisms in exons 1B and 1C of the type I

interleukin-1 receptor gene in patients with
endometriosis
Year: 2006
Author: P. D'Amora, H. Sato, M. J. Girao, I. D. Silva and E. Schor

Volume: 56
Issue: 3
Pages: 178-84
To study possible correlation between the prevalence of polymorphisms in the type I

interleukin-1 receptor gene and pelvic endometriosis. Genotypes of 223 women were
analyzed: 109 women with surgically and histologically confirmed endometriosis and
114 healthy women. Distributions of two single-base polymorphisms of the human
interleukin-1 receptor type I (IL-1RI) gene were evaluated: PstI, due to a C-->T
transition in exon 1B and BsrBI a C-->A transition at position 52 in exon 1C.
Polymorphisms were detected by polymerase chain reaction (PCR) followed by
restriction fragment length polymorphism analysis (RFLP) resolved on 3% agarose gels
stained with ethidium bromide. Genotypes for PstI polymorphisms did not differ
significantly among control and endometriosis (P = 0.058). However, in relation to BsrBI
polymorphism, protective risk was observed for the development of endometriosis [OR
0.39-IC 95% (0.2-0.9)]. BsrBI heterozygote genotype (C/A) showed protective effect
against endometriosis development.

Record Number: 59
Association study of endometriosis and intercellular

adhesion molecule-1 (ICAM-1) gene polymorphisms
in a Japanese population
Year: 2005
Author: M. Yamashita, S. Yoshida, S. Kennedy, N. Ohara, S. Motoyama and T. Maruo

Volume: 12
Issue: 4
Pages: 267-71
OBJECTIVE: Endometriosis is an immune-related, chronic inflammatory disease with

polygenic predisposition. Cell adhesion molecules are expressed in endometriotic
lesions, and in cells and tissues that are involved in the development and progression
of the disease. In this study, we investigated the possible association between
endometriosis and the G241R and K469E polymorphisms in the intercellular adhesion
molecule-1 (ICAM-1) gene in a Japanese population. METHODS: We compared the
distribution of the G241R and K469E polymorphisms in the ICAM-1 gene in 126
endometriosis patients and 172 controls using polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP) analysis in a Japanese population.
RESULTS: There were no significant differences between the cases and controls in the
allele frequencies or genotype distributions of either the G241R or K469E
polymorphisms in the ICAM-1 gene. The endometriosis patients were divided into a
subgroup of women with severe disease only. However, no significant differences were
observed in the allele frequencies and genotype distributions of the ICAM-1 K469E
polymorphisms between this subgroup and the controls. In contrast, only one in 169
controls was heterozygous (G/A genotype), and the A allele in the G241R
polymorphism was not found in any of the 126 endometriosis patients. CONCLUSION:
Our findings suggest that the G241R and K469E polymorphisms in the ICAM-1 gene
are unlikely to be associated with an increased risk of endometriosis in the Japanese
population.

Record Number: 64
Association between endometriosis and genetic

polymorphisms of the estradiol-synthesizing enzyme
genes HSD17B1 and CYP19
Year: 2005
Author: M. Tsuchiya, H. Nakao, T. Katoh, H. Sasaki, M. Hiroshima, T. Tanaka, T.

Matsunaga, T. Hanaoka, S. Tsugane and T. Ikenoue
Journal: Hum Reprod

Volume: 20
Issue: 4
Pages: 974-8
BACKGROUND: Endometriosis, an estrogen-dependent disease, is believed to be

influenced by multiple genetic and environmental factors. Here, we evaluated whether
the risk and severity of endometriosis are associated with polymorphisms in
estradiol-synthesizing enzyme genes: the Ser312Gly polymorphism in
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and the Arg264Cys
polymorphism in cytochrome P450, subfamily XIX (CYP19). METHODS: All
participants underwent diagnostic laparoscopy, and the stage of endometriosis was
determined according to the Revised American Fertility Society classification. Of the
138 women enrolled, 59 had no endometriosis, 21 had stage I, 10 had stage II, 23 had
stage III and 25 had stage IV. SNPs were discriminated by allele-specific
oligonucleotide hybridization. RESULTS: Individuals having at least one A-allele (A/G
or A/A genotype) of HSD17B1 showed a significantly increased risk of endometriosis (A
G genotype: adjusted OR, 3.06; 95%CI 1.21-7.74; A/A genotype: adjusted OR, 3.02;
95%CI 1.08-8.43). There was a significant trend associating A/G + A/A genotypes with
severity of endometriosis (P for trend < 0.01). No statistically significant association
was found for the CYP19 polymorphism. CONCLUSIONS: Evidence for association
between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a
Japanese population. The A-allele of HSD17B1 appears to confer higher risk for
endometriosis.

Record Number: 58
Analysis of the AhR, ARNT, and AhRR gene

polymorphisms: genetic contribution to
endometriosis susceptibility and severity
Year: 2005
Author: M. Tsuchiya, T. Katoh, H. Motoyama, H. Sasaki, S. Tsugane and T. Ikenoue

Volume: 84
Issue: 2
Pages: 454-8
OBJECTIVE: To explore whether polymorphisms in AhR, ARNT, and AhRR contribute

to endometriosis susceptibility and severity. DESIGN: Case control study. SETTING:
Hospital. PATIENT(S): One hundred thirty-eight Japanese women with or without
endometriosis, diagnosed endoscopically. INTERVENTION(S): Endoscopic
laparoscopy, with blood samples for genotyping obtained before the laparoscopic
examination for genomic DNA extraction from peripheral leukocytes. MAIN OUTCOME
MEASURE(S): AhR, ARNT, and AhRR polymorphisms were genotyped using real-time
polymerase chain reaction (PCR) analysis. Odds ratios and 95% confidence intervals
were calculated for AhR, ARNT, and AhRR genotypes to evaluate the risk of
endometriosis. Associations between these polymorphisms and stage of endometriosis
were also examined. RESULT(S): The C/G + G/G genotypes at codon 185 of AhRR
showed a statistically significant association with risk of endometriosis (adjusted odds
ratio, 2.53; 95% confidence interval, 1.16-5.55). Furthermore, a statistically significant
trend associated the C/G + G/G genotypes with the clinical stage of endometriosis. No
statistically significant association was observed between AhR codon 554 or ARNT
codon 189 polymorphisms and endometriosis. CONCLUSION(S): AhRR codon 185
polymorphism was associated with susceptibility to and severity of endometriosis in
Japanese women.

Record Number: 57
Association between polymorphisms in the

progesterone receptor gene and endometriosis
Year: 2005
Author: S. A. Treloar, Z. Z. Zhao, T. Armitage, D. L. Duffy, J. Wicks, D. T. O'Connor,

N. G. Martin and G. W. Montgomery

Volume: 11
Issue: 9
Pages: 641-7
The progesterone receptor (PR) is a candidate gene for the development of

endometriosis, a complex disease with strong hormonal features, common in women of
reproductive age. We typed the 306 base pair Alu insertion (AluIns) polymorphism in
intron G of PR in 101 individuals, estimated linkage disequilibrium (LD) between five
single-nucleotide polymorphisms (SNPs) across the PR locus in 980 Australian triads
(endometriosis case and two parents) and used transmission disequilibrium testing
(TDT) for association with endometriosis. The five SNPs showed strong pairwise LD,
and the AluIns was highly correlated with proximal SNPs rs1042839 (delta2 = 0.877,
D9 = 1.00, P < 0.0001) and rs500760 (delta2 = 0.438, D9 = 0.942, P < 0.0001). TDT
showed weak evidence of allelic association between endometriosis and rs500760 (P =
0.027) but not in the expected direction. We identified a common susceptibility
haplotype GGGCA across the five SNPs (P = 0.0167) in the whole sample, but
likelihood ratio testing of haplotype transmission and non-transmission of the AluIns
and flanking SNPs showed no significant pattern. Further, analysis of our results
pooled with those from two previous studies suggested that neither the T2 allele of the
AluIns nor the T1/T2 genotype was associated with endometriosis.

Record Number: 8
Polymorphisms in transforming growth

factor-beta-related genes ALK1 and ENG are
associated with sporadic brain arteriovenous
malformations
Year: 2005
Author: L. Pawlikowska, M. N. Tran, A. S. Achrol, C. Ha, E. Burchard, S. Choudhry, J.

Zaroff, M. T. Lawton, R. Castro, C. E. McCulloch, D. Marchuk, P. Y. Kwok and W. L.
Young
Journal: Stroke
Volume: 36
Issue: 10
Pages: 2278-80
BACKGROUND AND PURPOSE: Mutations in endoglin (ENG) and activin-like kinase

(ALK1) cause hereditary hemorrhagic telangiectasias, disorders characterized by
pulmonary and brain arteriovenous malformations (BAVMs). We investigated whether
polymorphisms in these genes are also associated with sporadic BAVM. METHODS: A
total of 177 sporadic BAVM patients and 129 controls (all subjects white) were
genotyped for 2 variants in ALK1 and 7 variants in ENG. RESULTS: The ALK1
IVS3-35A>G polymorphism was associated with BAVM: (AnyA [AA+AG] genotype:
odds ratio, 2.47; 95% CI, 1.38 to 4.44; P=0.002). Two ENG polymorphisms, ENG
-1742A>G and ENG 207G>A, showed a trend toward association with BAVM that did
not reach statistical significance. CONCLUSIONS: A common polymorphism in ALK1 is
associated with sporadic BAVM, suggesting that genetic variation in genes mutated in
familial BAVM syndromes may play a role in sporadic BAVMs.

Record Number: 3
Polymorphisms in transforming growth

factor-beta-related genes ALK1 and ENG are
associated with sporadic brain arteriovenous
malformations
Year: 2005
Author: L. Pawlikowska, M. N. Tran, A. S. Achrol, C. Ha, E. Burchard, S. Choudhry, J.

Zaroff, M. T. Lawton, R. Castro, C. E. McCulloch, D. Marchuk, P. Y. Kwok and W. L.
Young
Journal: Stroke
Volume: 36
Issue: 10
Pages: 2278-80
BACKGROUND AND PURPOSE: Mutations in endoglin (ENG) and activin-like kinase

(ALK1) cause hereditary hemorrhagic telangiectasias, disorders characterized by
pulmonary and brain arteriovenous malformations (BAVMs). We investigated whether
polymorphisms in these genes are also associated with sporadic BAVM. METHODS: A
total of 177 sporadic BAVM patients and 129 controls (all subjects white) were
genotyped for 2 variants in ALK1 and 7 variants in ENG. RESULTS: The ALK1
IVS3-35A>G polymorphism was associated with BAVM: (AnyA [AA+AG] genotype:
odds ratio, 2.47; 95% CI, 1.38 to 4.44; P=0.002). Two ENG polymorphisms, ENG
-1742A>G and ENG 207G>A, showed a trend toward association with BAVM that did
not reach statistical significance. CONCLUSIONS: A common polymorphism in ALK1 is
associated with sporadic BAVM, suggesting that genetic variation in genes mutated in
familial BAVM syndromes may play a role in sporadic BAVMs.

Record Number: 65
Polymorphisms of the genes encoding the GSTM1,

GSTT1 and GSTP1 in Korean women: no association
with endometriosis
Year: 2005
Author: S. E. Hur, J. Y. Lee, H. S. Moon and H. W. Chung

Volume: 11
Issue: 1
Pages: 15-9
Endometriosis, one of the most common gynaecologic disorders, shows significantly

elevated prevalence in industrial areas and there is also a possible genetic
predisposition. Glutathione-S-transferases (GSTs) are enzymes involved in the
metabolism of many disease-causing carcinogens and mutagens that are present in
human environments. An association between the incidence of endometriosis and the
GST genotypes of patients has been suggested. The objective of the present study
was to investigate whether the polymorphisms of GSTM1, GSTT1 and GSTP1 are
related to endometriosis. Blood samples were available from 259 controls and 194
patients with advanced endometriosis diagnosed by both pathology and laparoscopic
findings. The proportion of the GSTM1, GSTT1 and GSTP1 genotypes of the control
group were comparable to other populations. There was no significant evidence that
the distribution of the GSTM1 and GSTT1 genotype differed between the patients and
the controls, with an allelic odds ratio (OR)=1.074 [95% confidence interval
(CI)=0.737-1.564] and 1.239 (95% CI = 0.853-1.799), respectively. Also, there was no
significant difference in the proportion of GSTP1 genotypes between the women with
endometriosis and the control group with the OR = 0.823 (95% CI = 0.536-1.264). The
higher risk alleles were contended as GSTM1, GSTT1 null mutation and GSTP1
Ile105Ile polymorphism. There was no significant increase in the risk of endometriosis
as the number of higher risk alleles of the GST family increased. In conclusion, our
findings suggest that the GSTM1, GSTT1 and GSTP1 genetic polymorphisms are not
associated with the development of endometriosis in Korean women.

Record Number: 55
Ten estrogen-related polymorphisms and

endometriosis: a study of multiple gene-gene
interactions
Year: 2005
Author: A. Huber, C. C. Keck, L. A. Hefler, C. Schneeberger, J. C. Huber, E. K. Bentz

and C. B. Tempfer
Journal: Obstet Gynecol

Volume: 106
Issue: 5 Pt 1
Pages: 1025-31
OBJECTIVE: Genetic as well as hormonal factors are known to influence the

development and clinical course of endometriosis. We aimed to investigate the
association among 10 single nucleotide polymorphisms (SNPs) involved in the
estrogen metabolism and endometriosis and to develop a multiple genetic model.
METHODS: In a case-control study, we investigated the genotype frequencies of 10
estrogen metabolizing SNPs in 32 patients with endometriosis and 790 healthy controls
using sequencing-on-chip-technology with solid-phase polymerase chain reaction on
oligonucleotide microarrays: catechol-O-methyltransferase, Val158Met G->A,
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17), vlV A->C, cytochrome P450
(CYP), 17 A2 allele T->C, CYP1A1 MspI RFLP T->C, CYP1A1 Ile462Val A->G, CYP19
Arg264Cys C->T, CYP19 C1558T C->T, CYP 1B1 Leu432Val, CYP1B1 Asn453Ser,
and estrogen receptor alpha IVS1 -401>C. Associations and 2-way interaction models
between SNPs were calculated by stepwise logistic regression models. RESULTS: In a
univariate model, HSD17 vlV A->C was associated with a significantly increased risk of
endometriosis (P = .004; odds ratio 3.9, 95% confidence interval 1.6-9.8). When all
2-way interactions of investigated SNPs were ascertained, no significant interactions
among SNPs were observed. In a multivariate model, HSD17 vlV A->C was also
significantly associated with endometriosis (P = .002). CONCLUSION: We present data
on multiple SNPs in patients with endometriosis indicating an association between
HSD17 gene variation and the disease. Although not able to demonstrate interaction
models of SNPs, we provide evidence of HSD17 vlV A->C as a low penetrance genetic
marker of endometriosis. LEVEL OF EVIDENCE: II-2.

Record Number: 63
Estrogen receptor alpha dinucleotide repeat and

cytochrome P450c17alpha gene polymorphisms are
associated with susceptibility to endometriosis
Year: 2005
Author: Y. Y. Hsieh, C. C. Chang, F. J. Tsai, C. C. Lin and C. H. Tsai

Volume: 83
Issue: 3
Pages: 567-72
OBJECTIVE: To investigate the association of endometriosis with estrogen receptor

alpha (ER alpha) and cytochrome P450c17alpha (CYP17) gene polymorphisms in light
of the fact that estrogen plays a role in the pathogenesis of endometriosis and the
CYP17 enzyme is involved with estrogen biosynthesis. DESIGN: Prospective study.
SETTING: Genetics and gynecology units. PATIENT(S): All patients were divided into
two groups: group 1, women with endometriosis (n = 119); group 2, normal controls (n
= 108). INTERVENTION(S): A dinucleotide (thymine-adenine [TA]) repeat
polymorphism lying upstream of the ER alpha gene and A1/A2 polymorphism of the
CYP17 gene were amplified by polymerase chain reaction, enzyme restriction, and
electrophoresis. MAIN OUTCOME MEASURE(S): The ER genotypes were classified
into A through T (TA repeats, 10-29). The CYP17 genotypes included indigestible (A1
homozygote), heterozygote, and digestible (A2 homozygote). We compared these
polymorphism distributions in both groups. RESULT(S): The percentage of genotypes
D-G (TA, 13-16) in both groups were 10.5%, 29.4%, 13.0%, and 11.3% in group 1 and
7.9%, 16.7%, 19.9%, and 17.6% in group 2. The genotype E (14 TA repeats) is
associated with a higher risk of endometriosis. Proportions of A1 homozygote
heterozygote/A2 homozygote for CYP17 were 26.1%/46.2%/27.7% for group 1 and
14.8%/44.5%/40.7% for group 2, respectively. The A1 homozygote and allele were
associated with a higher susceptibility of endometriosis. CONCLUSION(S): ER alpha*
14 TA repeats and the CYP17* A1 allele are associated with an increased risk of
endometriosis. Both polymorphisms are useful markers for predicting endometriosis
susceptibility.

Record Number: 53
Glutathione S-transferases M1/T1 gene

polymorphisms and endometriosis: a meta-analysis
of genetic association studies
Year: 2005
Author: S. W. Guo

Volume: 11
Issue: 10
Pages: 729-43
In view of the controversies surrounding the glutathione S-transferases (GST) M1

T1-endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic
association studies of endometriosis was performed. In this meta-analysis involving 14
GSTM1 studies with 1539 cases and 1805 controls and nine GSTT1 studies with 746
cases and 834 controls, respectively, substantial heterogeneities among studies were
found. In addition, asymmetry in funnel plot was evident, which is likely to stem from
publication bias, given no apparent indication of true heterogeneity. The bias appears
to be prominent for GSTM1 studies, but is less so for GSTT1 studies. After correction
for this bias, there is no evidence that women with GSTM1 null genotype have
increased risk of developing endometriosis as compared with women with other
genotypes. For GSTT1, the risk associated with the null genotype is 29% higher than
other genotypes. However, even this estimate should be viewed with a large grain of
salt, because the estimate could easily lose its statistical significance if there is a
realistic 69-80% publication probability.

Record Number: 61
Polymorphisms in the promoter regions of FAS and

FASL genes as candidate genetic factors conferring
susceptibility to endometriosis
Year: 2005
Author: R. M. Fernandez, J. A. Noval, J. C. Garcia-Lozano, S. Borrego, J. L. Molini

and G. Antinolo
Journal: Int J Mol Med

Volume: 15
Issue: 5
Pages: 865-9
Although the pathophysiological mechanisms leading to endometriosis remain

unknown, several hypothesis have been proposed, including a dysregulation of the
normal apoptotic process which takes place in the endometrium. One of the apoptotic
pathways playing a crucial role in the programmed cell death within the endometrium is
the Fas-FasL system. In this study we have performed a case-control analysis in order
to evaluate three polymorphisms located within FAS (-1377G>A and -670A>G) and
FASL (-843C>T) genes, as susceptibility factors for endometriosis. We have analysed
a series of women with endometriosis compared respectively to a group of women
without symptoms of the disease, and to a group of confirmed unaffected women. The
genotyping of the three variants was carried out by Fluorescence Resonance Energy
Transfer (FRET) technology, and statistical analysis was performed using chi2 test with
Yates correction. Our results show that the differences in the distribution of the
polymorphic variants were not statistically significant when the group of patients was
compared to the other groups. Thus, it seems to indicate that the variants here
analysed are not involved in the pathogenesis of the disease in our population.
However this does not let us to completely exclude such genes as potential candidates
for the disease. A complete genetic analysis of the genes involved in the intricate
regulatory system of the apoptosis may lead to the identification of susceptibility factors
for the disease and a better understanding of its etiology.

Record Number: 62
Lack of association between endometriosis and

N-acetyl transferase 1 (NAT1) and 2 (NAT2)
polymorphisms in a Japanese population
Year: 2005
Author: M. Deguchi, S. Yoshida, S. Kennedy, N. Ohara, S. Motoyama and T. Maruo

Volume: 12
Issue: 3
Pages: 208-13
OBJECTIVE: We investigated the association between endometriosis and

polymorphisms in the N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2)
genes in a Japanese population, having previously demonstrated a positive association

with NAT2 polymorphisms in a UK population. METHODS: Genotyping for NAT1 alleles
*3, *4, *10, and *11, and NAT2 alleles *4, *5A, *5B, *5C, *6A, and *7B was performed
using polymerase chain reaction-restriction fragment-length polymorphism
(PCR-RFLP) and allele-specific PCR (AS-PCR) analysis in 145 ethnically Japanese,
endometriosis patients and 182 controls. The NAT1 and NAT2 allele and genotype
frequencies were compared in cases and controls using the Fisher exact test.
RESULTS: No significant differences between cases and controls were observed in the
frequencies of the NAT1 and NAT2 alleles (P = .13; P = .91) and genotypes (P = .24; P
= .79), and the NAT2 acetylation phenotypes (P = .46). Dividing the cases into a
subgroup, consisting of women with severe disease only (n = 80), had no effect on the
results. CONCLUSION: The distribution of NAT1 and NAT2 allele and genotype
frequencies were not significantly different between Japanese cases and controls. Our
findings suggest that polymorphisms in NAT1 and NAT2 are unlikely to be associated
with an increased risk of endometriosis in the Japanese population.

Record Number: 60
GSTM1, GSTT1 and CYP1A1 detoxification gene

polymorphisms and their relationship with advanced
stages of endometriosis in South Indian women
Year: 2005
Author: K. A. Babu, N. G. Reddy, M. Deendayal, S. Kennedy and S. Shivaji
Journal: Pharmacogenet Genomics

Volume: 15
Issue: 3
Pages: 167-72
OBJECTIVE(S): Studies on association between endometriosis and various phase I

and phase II detoxification genes such as glutathione S-transferase M1 and theta 1
(GSTM1 and GSTT1) and cytochrome P450 (CYP1A1) have produced inconsistent
results possibly because of ethnic differences. The present study was undertaken to
investigate the frequency of the CYP1A1 (6235T>C) polymorphism and GSTM1,
GSTT1 null mutations in a South Indian women's population with and without
endometriosis. METHODS: The frequencies of variants were studied in 310 women
with laparoscopically proven endometriosis (rAFS III=101; IV=209) and 215 women
without endometriosis using the polymerase chain reaction-restriction fragment length
polymorphism method. RESULTS: The GSTM1 null deletion showed significant
association (P=0.028) with endometriosis. No significant difference was found in the
frequencies of the GSTT1 null deletion in cases and controls. The frequencies of the
variant CYP1A1 homozygous and heterozygous alleles in the cases were 9% and
44.2% against 14.4% and 42.3% in the controls. Further, we observed a considerable
difference in the GSTM1 null deletion frequency in this population when compared with
other populations of the world. CONCLUSIONS: We observed an association between
endometriosis and the GSTM1 null deletion, but not with GSTT1 null deletions or the
CYP1A1 MspI polymorphism in South Indian women.

Record Number: 9
Novel mutations and polymorphisms in genes

causing hereditary hemorrhagic telangiectasia
Year: 2005
Author: S. A. Abdalla, U. Cymerman, D. Rushlow, N. Chen, G. P. Stoeber, E. G.

Lemire and M. Letarte
Journal: Hum Mutat

Volume: 25
Issue: 3
Pages: 320-1
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular

disorder caused by mutations in Endoglin (ENG) or activin receptor-like kinase-1
(ALK1, ACVRL1) genes. We performed molecular characterization in clinically affected
probands of 31 HHT families and detected a total of 28 different mutations in the two
genes, including four shared by more than one family. Twelve mutations were identified
in the ENG gene, six of which were novel and comprised two nonsense mutations in
exons 6 and 8, deletions in exons 5 and 11, and splice site mutations in exon 12 and
intron 8. Eleven of sixteen mutations identified in the ALK1 gene were novel single
base pair substitutions in exons 4, 7, 8, and 9. We also describe the first de novo ALK1
mutation that causes a previously unreported c.1133C>A substitution of a highly
conserved residue (p.P378H). The proband and his two daughters, who also carried
the familial mutation, all suffered from gastrointestinal (GI) bleeding. In addition, we
report seven newly identified polymorphisms and summarize all known ones in both
genes.

Record Number: 4
Novel mutations and polymorphisms in genes

causing hereditary hemorrhagic telangiectasia
Year: 2005
Author: S. A. Abdalla, U. Cymerman, D. Rushlow, N. Chen, G. P. Stoeber, E. G.

Lemire and M. Letarte
Journal: Hum Mutat

Volume: 25
Issue: 3
Pages: 320-1
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular

disorder caused by mutations in Endoglin (ENG) or activin receptor-like kinase-1
(ALK1, ACVRL1) genes. We performed molecular characterization in clinically affected
probands of 31 HHT families and detected a total of 28 different mutations in the two
genes, including four shared by more than one family. Twelve mutations were identified
in the ENG gene, six of which were novel and comprised two nonsense mutations in
exons 6 and 8, deletions in exons 5 and 11, and splice site mutations in exon 12 and
intron 8. Eleven of sixteen mutations identified in the ALK1 gene were novel single
base pair substitutions in exons 4, 7, 8, and 9. We also describe the first de novo ALK1
mutation that causes a previously unreported c.1133C>A substitution of a highly
conserved residue (p.P378H). The proband and his two daughters, who also carried
the familial mutation, all suffered from gastrointestinal (GI) bleeding. In addition, we
report seven newly identified polymorphisms and summarize all known ones in both
genes.

Record Number: 67
Polymorphisms in the estrogen receptor beta gene

but not estrogen receptor alpha gene affect the risk of
developing endometriosis in a Japanese population
Year: 2004
Author: Z. Wang, S. Yoshida, K. Negoro, S. Kennedy, D. Barlow and T. Maruo

Volume: 81
Issue: 6
Pages: 1650-6
OBJECTIVE: To determine whether polymorphisms in the estrogen receptor (ER)

alpha and beta genes are associated with endometriosis in a Japanese population.
DESIGN: Association study. SETTING: University hospital. PATIENT(S): Japanese
women diagnosed with endometriosis by laparotomy or laparoscopy.
INTERVENTION(S): Determination of polymorphisms in the ERalpha and ERbeta
genes was performed by polymerase chain reaction restriction fragment-length
polymorphism analysis in 132 affected women and 182 controls. MAIN OUTCOME
MEASURE(S): Frequency and distribution of AluI and RsaI polymorphisms in ERbeta
gene and of PvuII and XbaI polymorphisms in ERalpha gene. RESULT(S): No
significant differences in the frequency of either AluI and RsaI polymorphisms in the
ERbeta gene or of XbaI and PvuII polymorphisms in the ERalpha gene were found
between endometriosis patients and controls. However, a positive association was
noted between the AluI polymorphism in the ERbeta gene and stage IV endometriosis
patients in the population studied. CONCLUSION(S): The AluI polymorphism in the
ERbeta gene is associated with an increased risk of stage IV endometriosis in a
Japanese population.

Record Number: 66
Genetic contribution of tumor necrosis factor

(TNF)-alpha gene promoter (-1031, -863 and -857) and
TNF receptor 2 gene polymorphisms in endometriosis
susceptibility
Year: 2004
Author: M. Teramoto, J. Kitawaki, H. Koshiba, Y. Kitaoka, H. Obayashi, G. Hasegawa,

N. Nakamura, T. Yoshikawa, M. Matsushita, E. Maruya, H. Saji, M. Ohta and H. Honjo

Volume: 51
Issue: 5
Pages: 352-7
PROBLEM: Tumor necrosis factor (TNF)-alpha is a major cytokine involved in

inflammatory and immune function. The aim of this study was to investigate whether
polymorphisms at positions -1031, -863 and -857 in the TNF gene promoter region
(TNFA) and TNF receptor type 2 gene (TNFR2) are responsible in part for genetic
susceptibility to endometriosis. METHODS OF STUDY: TNFA and TNFR2
polymorphisms were determined in 123 patients with endometriosis and 165 fertile
healthy women by the polymerase chain reaction (PCR) - preferential homoduplex
formation assay and PCR-restriction fragment length polymorphism, respectively.
RESULTS: The frequency of the TNFA-U01 haplotype was increased significantly in
patients with endometriosis compared with controls (P = 0.045, OR = 1.45). The
TNFA-U01 haplotype was strongly associated with HLA-B*0702. No difference was
found in TNFR2 polymorphism between patients and controls. CONCLUSION: Our
results indicated that TNFA promoter polymorphism was associated with susceptibility
to endometriosis. However, this association was not independent of HLA-class I
polymorphisms.

Record Number: 68
Interferon-gamma gene dinucleotide (CA) repeat and

interleukin-4 promoter region (-590C/T)
polymorphisms in Japanese patients with
endometriosis
Year: 2004
Author: J. Kitawaki, H. Koshiba, Y. Kitaoka, M. Teramoto, G. Hasegawa, N.

Nakamura, T. Yoshikawa, M. Ohta, H. Obayashi and H. Honjo
Journal: Hum Reprod

Volume: 19
Issue: 8
Pages: 1765-9
BACKGROUND: Endometriosis is a multifactorial disease with possible genetic

predisposition and involvement of environmental factors in its pathogenesis. Cytokines
may play important roles in the pathogenesis of endometriosis. The aim of this study
was to investigate whether the interferon-gamma gene (IFNG) CA-repeat and
interleukin-4 (IL-4) promoter region (-590C/T) polymorphisms may be responsible in
part for genetic susceptibility to endometriosis. METHODS: IFNG CA-repeat and IL-4
-590C/T polymorphisms were determined for 185 patients with endometriosis and 176
healthy fertile women by quantitative genescan technology and PCR-restriction
fragment length polymorphism analysis, respectively. Patients with endometriosis were
analysed further according to their stage of disease, the presence or absence of
chocolate cysts and whether or not their disease was associated with adenomyosis and
or lyomyomata. RESULTS: The global IFNG allele frequencies in the patients with
endometriosis were significantly different from those in the control women (chi2 =
12.964, 6 df, P = 0.0436). The difference was due to an increase of the a13 (114 bp)
allele in patients with endometriosis (chi2 = 10.222, P = 0.0088, corrected P = 0.0352,
odds ratio = 1.48, 95% confidence interval = 1.10-1.98). There were no differences in
IL-4 -590C/T genotypes and allele frequencies between control women and all patients
with endometriosis or between control women and each subgroup of patients with
endometriosis. CONCLUSION: The results suggest that the IFNG CA-repeat
polymorphism is associated with susceptibility to endometriosis in a Japanese
population.

Record Number: 70
Intercellular adhesion molecule-1 (ICAM-1) gene

polymorphisms in endometriosis
Year: 2003
Author: P. Vigano, M. Infantino, D. Lattuada, R. Lauletta, E. Ponti, E. Somigliana, M.

Vignali and A. M. DiBlasio

Volume: 9
Issue: 1
Pages: 47-52
Endometriosis is a gynaecological disease with a certain genetic background, but the

locations of possible genomic aberrations are still poorly clarified. Intercellular adhesion
molecule-1 (ICAM-1), which is a surface glycoprotein that promotes adhesion in
immunological and inflammatory reactions, seems to play a role in this condition. The
aim of this study was to examine the potential associations of ICAM-1 gene
polymorphisms with endometriosis and its severity. Specifically, we have studied two
polymorphic sites located in codons 241 (G/R241) and 469 (E/K469) of the ICAM-1
gene. Three hundred and sixty-three Italian Caucasian women of reproductive age who
underwent laparoscopy for benign pelvic conditions were enrolled in the study.
Endometriosis was documented and staged in 188 women while 175 subjects, in whom
endometriosis was laparoscopically ruled out, served as the control group. The
frequency of the R241 allele was only marginally higher in endometriosis patients than
in controls [5.8 versus 2.9%, P = 0.05; odds ratio (OR), 2.1; 95% confidence interval
(CI), 1-4.5]. However, a strikingly high frequency of this allele was found in patients with
Stage IV endometriosis versus controls (8.6 versus 2.8%, P = 0.008; OR, 3.2; 95% CI,
1.3-7.9). In contrast, the allele and genotype frequencies of the E/K469 polymorphism
did not differ significantly between endometriosis and control groups. While the
functional correlate of the G/R241 polymorphism remains unclear, this finding indicates
that a genetic polymorphism in the ICAM-1 gene domain may contribute to the
susceptibility to endometriosis.

Record Number: 10
Endoglin gene mutations and polymorphisms in

Italian patients with hereditary haemorrhagic
telangiectasia
Year: 2003
Author: P. Lastella, C. Sabba, G. M. Lenato, N. Resta, W. Lattanzi, M. Gallitelli, A.

Cirulli and G. Guanti
Journal: Clin Genet

Volume: 63
Issue: 6
Pages: 536-40
Autosomal-dominant hereditary haemorrhagic telangiectasia (HHT) is a genetically

heterogeneous disease caused by mutations in at least two different loci. We screened
for mutations in four Italian families where segregation studies showed clear evidence
of linkage to the endoglin (ENG) locus. In addition, one sporadic case and three
patients with pulmonary arteriovenous malformations, belonging to small nuclear
families unsuitable for linkage analysis, were included in the screening. The proband
from each family was investigated using single-strand conformation polymorphism and
heteroduplex analysis; potential variants were sequenced. Four novel and one
previously reported mutation were detected, as well as three new polymorphisms. The
novel mutations included deletions in exon 1 (patient 581/02), exon 5 (patient 780/01)
and exon 7 (patient 700/01), and a C-->T229 substitution in exon 3 (patient 462/02).
When analysing patient 700/01 and his affected daughter, we encountered a mutant
ENG allele with two mutations--a deletion in exon 7 and a substitution in exon
12--which converts isoleucine 575 into threonine, in a non-conserved region. Both
mutations were absent in the two healthy sons of the patient, while the polymorphic
variant in exon 12 was present in his healthy father. These results and
haplotype-segregation studies suggest that a de novo deletion had occurred in the
gamete of paternal origin. For the first time the parental germline in which a de novo
HHT mutation occurred has been identified.

Record Number: 5
Endoglin gene mutations and polymorphisms in

Italian patients with hereditary haemorrhagic
telangiectasia
Year: 2003
Author: P. Lastella, C. Sabba, G. M. Lenato, N. Resta, W. Lattanzi, M. Gallitelli, A.

Cirulli and G. Guanti
Journal: Clin Genet

Volume: 63
Issue: 6
Pages: 536-40
Autosomal-dominant hereditary haemorrhagic telangiectasia (HHT) is a genetically

heterogeneous disease caused by mutations in at least two different loci. We screened
for mutations in four Italian families where segregation studies showed clear evidence
of linkage to the endoglin (ENG) locus. In addition, one sporadic case and three
patients with pulmonary arteriovenous malformations, belonging to small nuclear
families unsuitable for linkage analysis, were included in the screening. The proband
from each family was investigated using single-strand conformation polymorphism and
heteroduplex analysis; potential variants were sequenced. Four novel and one
previously reported mutation were detected, as well as three new polymorphisms. The
novel mutations included deletions in exon 1 (patient 581/02), exon 5 (patient 780/01)
and exon 7 (patient 700/01), and a C-->T229 substitution in exon 3 (patient 462/02).
When analysing patient 700/01 and his affected daughter, we encountered a mutant
ENG allele with two mutations--a deletion in exon 7 and a substitution in exon
12--which converts isoleucine 575 into threonine, in a non-conserved region. Both
mutations were absent in the two healthy sons of the patient, while the polymorphic
variant in exon 12 was present in his healthy father. These results and
haplotype-segregation studies suggest that a de novo deletion had occurred in the
gamete of paternal origin. For the first time the parental germline in which a de novo
HHT mutation occurred has been identified.

Record Number: 69
CYP1A1, CYP19, and GSTM1 polymorphisms increase

the risk of endometriosis
Year: 2003
Author: D. A. Arvanitis, G. E. Koumantakis, A. G. Goumenou, I. M. Matalliotakis, E. E.

Koumantakis and D. A. Spandidos

Volume: 79 Suppl 1
Pages: 702-9
OBJECTIVE: To investigate the possibility of genetic contribution of CYP1A1, CYP19,

GSTM1, and GSTT1 polymorphisms to endometriosis. DESIGN: Genetic polymorphism
analysis. SETTING: Case-control study. PATIENT(S): A group of 275 women with
sporadic endometriosis was compared with a group of 346 fertile, endometriosis-free
women. INTERVENTION(S): Surgical, laparoscopic, and histological examination.
MAIN OUTCOME MEASURE(S): Blood specimens were obtained from endometriosis
cases and controls. Polymerase chain reaction-based assays were performed for the
determination of individual's genotype. RESULT(S): The CYP19 VNTR, located in
intron 4 (TTTA)(10) allele increases the risk for endometriosis development (odds ratio
[OR], 4.99; 95% confidence interval [95% CI], 1.351 to 18.436). The combined
genotype CYP1A1 wt/m1 or m1/m1 and GSTM1 null deletion adds to this risk (OR,
1.95; 95% CI, 1.266 to 2.995 and OR, 2.23; 95% CI, 0.631 to 7.906, respectively). In
contrast, the CYP1A1 wt/wt genotype exhibits a protective effect, with a 38% reduction
in the odds for endometriosis development (OR, 0.62; 95% CI, 0.440 to 0.883).
CONCLUSION(S): Our data suggest that CYP19 VNTR (TTTA)(10) allele as well as
the combined genotype CYP1A1 m1 polymorphism and GSTM1 null deletion associate
with the endometriosis phenotype, whereas the GSTT1 null deletion does not.

Record Number: 71
Tumor necrosis factor-alpha promotor

polymorphisms and endometriosis
Year: 2002
Author: F. Wieser, G. Fabjani, C. Tempfer, C. Schneeberger, R. Zeillinger, J. C. Huber

and R. Wenzl

Volume: 9
Issue: 5
Pages: 313-8
To explore whether having the mutant tumor necrosis factor (TNF)2 (G-308*A) and
TNFA-A (G-238*A) alleles in the TNF-alpha gene promotor region is higher in women
with endometriosis, we determined the respective genotype and allele frequencies in a
retrospective case-control study. Polymerase chain reaction was performed to identify
the G-308A and G-238A promotor polymorphisms in 92 women with surgically and
histologically confirmed endometriosis. A series of 69 healthy women without a history
of endometriosis served as clinical controls. The allele frequencies of the TNF2
polymorphism were 0.13 and 0.16 in women with endometriosis and in the control
group, respectively, and the frequencies of the TNFA-A polymorphisms in women with
endometriosis and in the control group were 0.04 and 0.05, respectively, with no
significant difference between the study and control groups. The TNF2 polymorphism
was present in the homozygous form (TNF(2/2)) in 4.3% of women with endometriosis
and in 2.9% of controls (P=.7). No TNFA-A homozygotes (TNFA(A/A)) were detected.
We studied TNF-alpha promotor gene variants among women with endometriosis and
found that having the G-308A TNF-alpha and the G-238A TNF-alpha polymorphism
was not associated with endometriosis in a white population.

Record Number: 72
[Susceptibility to endometriosis in women of Han

Nationality in Guangdong Province associated with
Msp I polymorphisms of cytochrome P450 1A1 gene]
Year: 2002
Author: D. X. Peng, Y. L. He, L. W. Qiu, F. Yang and J. M. Lin
Journal: Di Yi Jun Yi Da Xue Xue Bao

Volume: 22
Issue: 9
Pages: 814-6
OBJECTIVE: To assess the possible association of the Msp I polymorphisms of

cytochrome P4501A1(CYP1A1) gene with the susceptibility to endometriosis in women
of Han Nationality in Guangdong Province. METHODS: Polymerase chain
reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to
analyze the 3 genotypes m1m1, m1m2 and m2m2 in 3'-flanking region of CYP1A1 in
76 patients with endometriosis and 80 healthy controls. RESULTS: The frequencies of

genotypes m1m1, m1m2 and m2m2 were 30.3 %, 50.0 % and 19.7 % in patients with
endometriosis while 42.5 %, 45.0 % and 12.5 % in the controls, respectively, showing
no statistically significant difference in the frequencies of the three genotypes between
the 2 groups. The frequencies of two alleles were of no significant difference between
the patients and controls, either. CONCLUSION: Msp I polymorphisms of cytochrome
P4501A1 in itself might not be associated with the susceptibility to endometriosis in
women of Han Nationality in Guangdong Province.

Record Number: 73
Tumor necrosis factor-alpha and interleukin-6

promoter gene polymorphisms are not associated
with an increased risk of endometriosis
Year: 2002
Author: M. K. Lee, A. J. Park and D. H. Kim

Volume: 77
Issue: 6
Pages: 1304-5

Record Number: 75
Association of the CYP17 gene and CYP19 gene

polymorphisms with risk of endometriosis in
Japanese women
Year: 2002
Author: N. Kado, J. Kitawaki, H. Obayashi, H. Ishihara, H. Koshiba, I. Kusuki, K.

Tsukamoto, G. Hasegawa, N. Nakamura, T. Yoshikawa and H. Honjo
Journal: Hum Reprod

Volume: 17
Issue: 4
Pages: 897-902
BACKGROUND: To investigate whether polymorphisms of CYP17 and CYP19 genes

are associated with the risk of endometriosis, we analysed the frequency and
distribution of a single nucleotide polymorphism at the 5' untranslated region of the
CYP17 gene, and a tetranucleotide (TTTA) tandem repeat polymorphism and a 3 bp
insertion (I)/deletion (D) polymorphism in intron 4 of the CYP19 gene. METHODS: We
studied 140 patients with endometriosis, 67 with adenomyosis and/or leiomyomas and
177 healthy control women. RESULTS: The distribution of the genotypes of CYP17 and
alleles of the TTTA repeat polymorphism of CYP19 were not significantly different
between the groups. In contrast, an increased frequency of the D/D genotype was
observed in the endometriosis group as compared with the control group (D/D
genotype versus I/I plus I/D genotypes; corrected P = 0.024). This was more evident in
the endometriosis subgroups with chocolate cysts (corrected P = 0.043) and at severe
clinical stages (corrected P = 0.035). CONCLUSIONS: The results suggest that the 3
bp I/D polymorphism of the CYP19 gene may be weakly associated with the
susceptibility of endometriosis in a Japanese population.

Record Number: 74
Polymorphisms for interleukin-4 (IL-4) -590 promoter,

IL-4 intron3, and tumor necrosis factor alpha -308
promoter: non-association with endometriosis
Year: 2002
Author: Y. Y. Hsieh, C. C. Chang, F. J. Tsai, Y. Hsu, H. D. Tsai and C. H. Tsai
Journal: J Clin Lab Anal

Volume: 16
Issue: 3
Pages: 121-6
Interleukin-4 (IL-4) is a cytokine with anti-inflammatory properties. Tumor necrosis

factor alpha (TNF-alpha), a pluripotent proinflammatory cytokine, plays an important
role in the process of numerous inflammatory and autoimmune diseases. We aimed to
investigate whether gene polymorphisms for the IL-4 -590 promoter, IL-4 intron3 and
TNFalpha -308 promoter could be used as markers of susceptibility in endometriosis.
The subjects, 226 premenopausal Taiwan Chinese women with surgically diagnosed
endometriosis and nonendometriosis, were divided into two groups: 1) endometriosis (n

= 120) and 2) nonendometriosis (n = 106). Polymorphisms for the IL-4 -590 promoter,
IL-4 intron3, and TNFalpha -308 G-to-A promoter were detected by polymerase chain
reaction (PCR). Genotypes and allelic frequencies for these gene polymorphisms in
both groups were compared. We observed no significant differences in genotype
distribution and allele frequency of the IL-4 -590 promoter, IL-4 intron3, and TNFalpha
gene polymorphism between both groups. The proportions of the -590*C homozygote
heterozygote/-590* T homozygote for the IL-4 promoter in both groups were 1.6/31.6
66.6% in group 1, and 5.8/33.0/61.2% in group 2. The proportions of the RP1
homozygote/heterozygote/RP2 homozygote for IL-4 intron3 in both groups were 62.5
34.1/2.5% (group 1), and 64.1/32.0/3.9% (group 2). The proportions of -308*A
homozygote/heterozygote/-308*G homozygote for the TNFalpha promoter in both
groups were 7.5/20.8/71.7% (group 1), and 7.5/17/75.5% (group 2). We concluded that
there is no association between endometriosis and the IL-4 and TNFalpha gene
polymorphisms. The IL-4 -590 promoter, IL-4 intron3, and TNFalpha -308 G-to-A
polymorphisms are not useful markers for predicting susceptibility to endometriosis.

Record Number: 76
Association between endometriosis and N-acetyl

transferase 2 polymorphisms in a UK population
Year: 2001
Author: S. Nakago, R. M. Hadfield, K. T. Zondervan, H. Mardon, S. Manek, D. E.

Weeks, D. Barlow and S. Kennedy

Volume: 7
Issue: 11
Pages: 1079-83
The relationship between endometriosis and polymorphisms in the N-acetyl transferase

2 (NAT 2) gene was investigated in a UK population, as this gene has been previously
implicated in the aetiology of the disease. Point mutations in the gene result in the
variant alleles NAT 2 *5, *6 and *7 from the wild-type NAT 2 *4 allele. Homozygotes for
the NAT 2 *4 wild type allele are fast NAT acetylators, while heterozygotes with one
wild-type allele and a variant NAT 2 *5, *6 or *7 allele have reduced enzyme activity,
and individuals with two variant alleles are slow acetylators. The NAT 2 *4/*6 genotype
was significantly more common among affected women (35.2%) than population
controls (8.1%; P = 0.0001) or unaffected women (4.2%; P = 0.02). Significantly more
affected women (57.4%) were fast acetylators than were population controls (32.3%; P
< 0.01) or unaffected women (33.3%; P < 0.05). These data suggest that altered NAT 2
enzyme activity may be a predisposition factor in endometriosis, or that NAT 2 alleles
may be in linkage disequilibrium with a susceptibility allele in the same chromosomal
region.

Record Number: 77
Polymorphisms for interleukin-1 beta (IL-1 beta)-511

promoter, IL-1 beta exon 5, and IL-1 receptor
antagonist: nonassociation with endometriosis
Year: 2001
Author: Y. Y. Hsieh, C. C. Chang, F. J. Tsai, J. Y. Wu, Y. R. Shi, H. D. Tsai and C. H.

Tsai
Journal: J Assist Reprod Genet

Volume: 18
Issue: 9
Pages: 506-11
PURPOSE: We aimed to investigate if interleukin-1 beta (IL-1 beta) and IL-1 receptor
antagonist (IL-1Ra) gene polymorphism could be used as markers of susceptibility in
endometriosis. MATERIALS AND METHODS: Women were divided into two groups: 1)
endometriosis (n = 120); 2) nonendometriosis groups (n = 103). Polymorphisms for IL-1
beta-511 promoter, IL-1 beta exon 5, and IL-1Ra were detected by polymerase chain
reaction. Genotypes and allelic frequencies for these polymorphisms in both groups
were compared. RESULTS: Proportions of different IL-1 and IL-1Ra polymorphisms in
both groups were nonsignificantly different. Proportions of C homozygote/heterozygote
T homozygote for IL-1 beta-511 promoter in both groups were 1) 21.6/59.1/19.1% and
2) 26.2/50.5/23.3%. Proportions of E1 homozygote/heterozygote/E2 homozygote for
IL-1 beta exon 5 in both groups were 1) 91.6/5/3.3% and 2) 95.15/4.85/0%. Allele I/II/IV
V for IL-1Ra in both groups were 1) 92.5/5.4/1.6/0.4% and 2) 95.1/3.9/1/0%.
CONCLUSIONS: Association of endometriosis with IL-1 beta-511 promoter, IL-1 beta
exon 5, and IL-1 receptor antagonist gene polymorphisms doesn't exist. These
polymorphisms are not useful markers for prediction of endometriosis susceptibility.

Record Number: 78
Association of estrogen receptor gene

polymorphisms with endometriosis
Year: 1999
Author: I. Georgiou, M. Syrrou, I. Bouba, N. Dalkalitsis, M. Paschopoulos, I.

Navrozoglou and D. Lolis

Volume: 72
Issue: 1
Pages: 164-6
OBJECTIVE: To explore the association of the estrogen receptor two-allele (point)

polymorphism and multiallele (microsatellite) polymorphism with endometriosis.
DESIGN: Case-control study. SETTING: Genetics and Endoscopy Unit, Department of
Obstetrics and Gynecology, Ioannina University HOSPITAL, Ioannina, Greece.
PATIENT(S): Fifty-seven women with surgically and histologically diagnosed
endometriosis of stages I-IV. INTERVENTION(S): Diagnostic laparoscopy. MAIN
OUTCOME MEASURE(S): Frequency and distribution of the estrogen receptor gene
polymorphisms. RESULT(S): There was a statistically significant difference between
the patients and the controls in the frequency of the two-allele Pvu II polymorphism
(0.72 vs. 0.49) and in the median repeats of the (TA)n multiallele polymorphism (15 vs.
20 repeats). In both groups, linkage was found between the fewer (TA)n repeats
(range, 12-19) and the positive Pvu II polymorphism. CONCLUSION(S): The variability
of the estrogen receptor gene likely contributes to the pathogenesis of endometriosis.

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