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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.
Polymorfism endoglin.enl Page 3
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.
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
Polymorfism endoglin.enl Page 4
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.
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.
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
Author: J. Xie, S. Wang, B. He, Y. Pan, Y. Li, Q. Zeng, H. Jiang and J. Chen
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.
Author: Q. Liu, Y. Li, J. Zhao, R. M. Zhou, N. Wang, D. L. Sun, Y. N. Duan and S. Kang
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.
Author: Q. Liu, Y. Li, J. Zhao, D. L. Sun, Y. N. Duan, N. Wang, R. M. Zhou and S. Kang
endometriosis. The -1154A and -2578A alleles may be protective against the
development of endometriosis in North Chinese women.
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.
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.
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.
Year: 2008
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: 22
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.
Year: 2008
Pages: 399-404
Journal: Reproduction
Volume: 134
Issue: 2
Pages: 373-8
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.
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: 35
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.
similar tendency was also observed in the GSTT1 allele distribution. CONCLUSION:
Genetic factors could modify the response to environmental pollutants in endometriosis.
Journal: Reproduction
Volume: 131
Issue: 1
Pages: 153-61
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.
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.
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.
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.
Author: S. W. Guo
Author: S. W. Guo
Year: 2005
Pages: 641-7
Journal: Stroke
Volume: 36
Issue: 10
Pages: 2278-80
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.
Journal: Stroke
Volume: 36
Issue: 10
Pages: 2278-80
Author: S. W. Guo
Volume: 15
Issue: 5
Pages: 865-9
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.
Volume: 81
Issue: 6
Pages: 1650-6
(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.
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.
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.
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.
Volume: 17
Issue: 4
Pages: 897-902
< 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.
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.