ESR1 PvuII Research Articles

Association of Estrogen Receptor-α and Aryl Hydrocarbon Receptor Gene Polymorphisms with Ischemic Stroke in an Egyptian Population: A Pilot Study.

Stroke is the second leading cause of death and a major contributor to disability worldwide, with the highest prevalence in developing countries. Ischemic stroke (IS) is a complex disease resulting from genetic and environmental interactions. The present work is a pilot study exploring the association of estrogen receptor-α (ESR1) and aryl hydrocarbon receptor (AHR) SNPs with IS in a small Egyptian population of IS patients. Sixty IS patients and 60 matched healthy controls were included in this case-control study. Genotyping of ESR1 PvuII (rs2234693), ESR1 XbaI (rs9340799), and AHR rs2066853 SNPs was performed using real-time PCR. ESR1 PvuII TC and CC genotypes were associated with IS (odds ratio (OR) = 2.821, 95% confidence interval (CI) = 1.204-6.609, p = 0.017, and OR = 9.455, 95% CI = 2.222-40.237, p = 0.002, respectively), and TC genotype in female IS (OR = 4.018, 95% CI = 1.117-14.455, p = 0.033). Additionally, ESR1 XbaI GA and GG genotypes were associated with IS (OR = 2.833, 95% CI = 1.190-6.749, p = 0.019, and OR = 34.000, 95% CI = 6.965-165.980, p < 0.001, respectively), and the AG and GG genotypes in male IS (OR = 3.378, 95% CI = 1.103-10.347, p = 0.033 and OR = 22.8, 95% CI = 2.580-201.488, p = 0.005, respectively) and the GG genotype in female IS (95% CI = 7.259-1115.914, p < 0.001). ESR1 PvuII and XbaI haplotypes C-A, T-G, and C-A increased the risk of ISin both genders, in male IS, and in female IS apart from C-A. The AG genotype of AHR rs2066853 was associated with male IS (OR = 6.900, 95% CI = 2.120-22.457 p = 0.001). ESR1 PvuII, ESR1 XbaI, and AHR rs2066853 SNPs are associated with IS in Egyptians. However, this is a small sample, and the findings should be replicated in a larger population.

ESR1 rs2234693 might be associated with TMD risk in the Turkish population, but not rs9340799

Aims: The gender and age distribution of temporomandibular disorder (TMD) suggest a possible role for the female hormonal axis in the pathogenesis. The goal of this study was to evaluate if estrogen receptor (ESR1) gene variants contribute to TMD susceptibility in the Turkish population. Methods: A total of 270 people, 130 of whom were TMD patients and 140 healthy controls, were included in the study. The ESR1 PvuII (rs2234693) and Xbal (rs9340799) variants were genotyped using the polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP). The results were evaluated statistically. Results: There were 110 women (81.48%) and 25 men (18.52%) in the patient group. We found there was a significant association between rs2234693 T/C, C/C genotypes and TMD (p=0.007). Also, the C allele was more prevalent in patients compared to controls (p=0.002). A statistically significant association was observed when the patients were compared with the controls according to TT versus TC+CC (p=0.002). There was no statistical significance between the patient and control groups in terms of rs9340799 genotype and allele distribution. Then we evaluated the relationship between genotype distributions and clinical characteristics. Both males and females had the highest rs2234693 T/C genotype (p=0.049). The majority of people with bruxism, bruxomania, and bruxism plus bruxoma carried the rs2234693 T/C genotype (p=0.025). Conclusion: Our results showed that ESR1 rs2234693 might be associated with TMD risk in the Turkish population, but not rs9340799.

Association between the ESR1 and ESR2 polymorphisms and osteoporosis risk: An updated meta-analysis.

Gene polymorphisms of estrogen receptor (ESR) 1 PvuII (rs2234693), XbaI (rs9340799), G2014A (rs2228480), ESR2 AluI (rs4986938), and RsaI (rs1256049) had been reported to be associated with the risk of osteoporosis. However, these conclusions were inconsistent, therefore, an updated meta-analysis was conducted to further explore these issues. To evaluate the association between gene polymorphisms of ESR1 PvuII (rs2234693), XbaI (rs9340799), G2014A (rs2228480), ESR2 AluI (rs4986938), RsaI (rs1256049), and osteoporosis risk. PubMed, Medline, Ovid, Embase, CNKI, and China Wanfang databases were searched. Association was assessed using odds ratio with 95% confidence interval. Moreover, the false-positive reporting probability, Bayesian false-finding probability, and Venetian criteria were used to assess the credibility of statistically significant associations. Overall, ESR1 PvuII (rs2234693) and XbaI (rs9340799) were associated with the risk of osteoporosis in Indians. Moreover, ESR1 G2014A (rs2228480) was associated with the decreased risk of osteoporosis in East Asians. Moreover, ESR2 Alul (rs4986938) was associated with the increased risk of osteoporosis in East Asians and Caucasians. There was a significant association between ESR2 Rsal (rs1256049) and osteoporosis risk in overall population. When only high-quality and Hardy-Weinberg equilibrium studies were included in the sensitivity analysis, all results did not change in the present study. When the credibility was evaluated applying false-positive reporting probability, Bayesian false-finding probability, and Venetian criteria, all significant associations were considered as false positive results. In summary, this study shows that all substantial associations between gene polymorphisms of ESR1 (PvuII, XbaI, and G2014A) and ESR 2 (AluI and RsaI) and osteoporosis risk are possibly false positive results instead of real associations or biological variables.

Association of ESR1 and ESR2 Polymorphisms with Osteoporosis: A Meta-Analysis from 36 Studies

Background: Recently, the roles of ESR1 and ESR2 polymorphisms in osteoporosis have been extensively reported, with conflicting findings. Therefore, we performed this present study to evaluate the potential associations between ESR1 and ESR2 polymorphisms and osteoporosis risk. Methodology: All included literatures published up to April 2021 were identified by searching Pubmed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated the associations using a fixed or random effects model. Results: 36 observational studies involving five gene polymorphisms (ESR1 PvuII, ESR1 XbaI, ESR1 G2014A, ESR2 AluI and ESR2 RsaI) covering 12507 cases and 18487 controls were included. The results of our meta-analysis demonstrated the variant A allele of ESR2 RsaI polymorphism might play a remarkable protective role in developing osteoporosis under all genetic models. However, no associations were observed between ESR1 PvuII, ESR1 XbaI, ESR1 G2014A and ESR2 AluI polymorphisms with the risk of osteoporosis under all genetic models. Conclusions: Our meta-analysis suggests that genetic polymorphism in ESR2 RsaI may lead to decreased risk for osteoporosis. Further larger studies are needed to confirm this conclusion.

ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer

BackgroundThe ESR1 gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene called ESR1 PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate the ESR1 PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer.MethodsThis retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. The ESR1 PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples.ResultsThe percentages of patients with ESR1 PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients with ESR1 PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05–3.04; p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days).ConclusionThe ESR1 PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.

Estrogen receptor alpha XbaI polymorphism is associated with higher relaxin-3 levels in women with metabolic syndrome

Relaxin-3 is known to play a role in appetite regulation, increasing food intake and body weight. This study aimed to assess the relation of relaxin-3 with ERS1 XbaI and PvuII polymorphisms. One hundred female patients with metabolic syndrome were investigated. The genotypes of ESR1 XbaI and PvuII polymorphisms were assessed with PCR-RFLP. Serum relaxin-3 level was measured for all participants using ELISA. Higher relaxin-3 levels showed association with the minor GG genotype of ESR-1 XbaI polymorphism but not PvuII polymorphism.

ESR1 PvuII (rs2234693 T>C) polymorphism and cancer susceptibility: Evidence from 80 studies.

Emerging epidemiological researches have been performed to assess the association of ESR1 PvuII (rs2234693 T>C) polymorphism with the risk of cancer, yet with conflicting conclusions. Therefore, this updated meta-analysis was performed to make a more accurate evaluation of such relationship. We adopted EMBASE, PubMed, CNKI, and WANFANG database to search relevant literature before January 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were employed to estimate the relationship strengths. In final, 80 studies (69 publications) involving 26428 cases and 43381 controls were enrolled. Our results failed to provide significant association between overall cancer risk and PvuII polymorphism under homozygous (TT vs. CC) and heterozygous (TT vs. CT) models. Statistically significant relationship was only observed for PvuII polymorphism in allele model T vs. C (OR=0.95, 95% CI=0.91-0.99). Stratification analysis by cancer type suggested that T genotype significantly decreased prostate cancer risk (TT vs. CC: OR=0.79, 95% CI=0.66-0.94; T vs. C: OR=0.89, 95% CI=0.82-0.98), Leiomyoma risk (T vs. C: OR=0.82, 95% CI=0.68-0.98), and HCC risk (TT vs. CC: OR=0.45, 95% CI=0.28-0.71; T vs. C: OR=0.67, 95% CI=0.47-0.95). Furthermore, significantly decreased risk was also found for Africans, population-based and hospital-based studies in the stratified analyses. These results suggest that ESR1 PvuII (rs2234693 T>C) polymorphism may only have little impact on cancer susceptibility. In the future, large-scale epidemical studies are warranted to verify these results.

The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea

ABSTRACTPrimary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case–control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration.

Influence of vitamin D and estrogen receptor gene polymorphisms on calcium absorption: BsmI predicts a greater decrease during energy restriction

Low calcium absorption is associated with low bone mass and fracture. In this study, we use gold standard methods of fractional calcium absorption (FCA) to determine whether polymorphisms of intestinal receptors, vitamin D receptor (VDR) and estrogen receptor α (ESR1), influence the response to energy restriction. Fractional calcium absorption was measured using dual stable isotopes (42Ca and 43Ca) in women given adequate calcium and vitamin D and examined at baseline and after 6weeks of energy restriction or no intervention. After genotyping, the relationship between VDR and ESR1 genotypes/haplotypes and FCA response was assessed using several genetic models. One-hundred and sixty-eight women (53±11years of age) were included in this analysis. The ESR1 polymorphisms, PvuII and XbaI and VDR polymorphisms (TaqI, ApaI) did not significantly influence FCA. The BB genotype of the VDR polymorphism, BsmI, was associated with a greater decrease in FCA than the Bb/bb genotype. Multiple linear regression showed that the BsmI polymorphism or the VDR haplotype, BAt, in addition to changes in weight and vitamin D intake explained ~16% of the variation in changes in FCA. In conclusion, the reduction in calcium absorption due to energy restriction is greatest for those with the BB genotype. Previous candidate gene studies show that VDR polymorphisms are associated with higher risk for osteoporosis, and the current study supports the notion that the BsmI polymorphism in intestinal VDR may be contributing to alterations in bone health.

Estrogen receptors 1 and 2 genotypes and age at menarche in idiopathic scoliosis

Objectives The age at menarche (AAM) is commonly in use in patients with IS as one of the maturity indicator suggesting deceleration of the growth velocity. The AAM was suggested to be related to predisposition and curve progression potential of IS. The late age at menarche was reported to be associated with higher prevalence of adolescent idiopathic scoliosis. The age at menarche is determined by both genetic and environmental factors as well as their interactions. Estrogen receptors 1 and 2 polymorphism were reported to be associated with AAM: in ESR1 XbaI and PvuII site polymorphism and in ESR2 AluI site polymorphism. The purpose of the study was to investigate associations of the ESR1 and ESR2 polymorphisms with AAM in IS patients.

Estrogen receptors genes polymorphisms and age at menarche in idiopathic scoliosis.

BackgroundThe age at menarche (AAM) is commonly in use in patients with IS as one of the maturity indicator suggesting deceleration of the growth velocity. The AAM was suggested to be related to predisposition and curve progression potential of IS. The late age at menarche was reported to be associated with higher prevalence of adolescent idiopathic scoliosis. The age at menarche is determined by both genetic and environmental factors as well as their interactions. Estrogen receptors 1 and 2 polymorphism were reported to be associated with AAM: in ESR1 XbaI and PvuII site polymorphism and in ESR2 AluI site polymorphism.The purpose of the study was to investigate associations of the ESR1 and ESR2 polymorphisms with AAM in IS patients and to evaluate association of AAM with IS severity.Methods208 females with IS Caucasian females from Central Europe underwent clinical, radiological and genetic examinations. Four SNPs were selected XbaI (A/Grs9340799) and PvuII (C/T rs2234693) in ESR1 and AluI (A/G rs4986938) and RasI (A/G rs1256049) in ESR2. Samples were analyzed with polymerase chain reaction followed by restriction fragments length polymorphism analysis (PCR-RFLP). The age of a menarche was established during personal interview with the patients and in case of children with their parents. The Cobb angle was measured.ResultsAll genotypes followed HWE. Mean AAM for patients was 154.8 ± 14.7 months (12.9 ± 1.2 years). The earliest AAM was 121 and latest 192 months. There was no statistically significant difference between AAM mean values in each genotype, for the XbaI, PvuII, AluI and RsaI site polymorphisms the p values were p = 0.7141, p = 0.9774, p = 0.7973 and p = 0.2282, respectively. Patients divided according to Cobb into mild (<30°), moderate (30°-49°) or severe (≥50°) IS revealed tendency to delay AAM: 151.9 ± 14.7; 155.2 ± 14.8 and 157.9 ± 14.0 months, respectively. There was statistical significant difference between patients with mild <30° and severe ≥50° IS, p = 0.0267.ConclusionsIn IS patients estrogen receptors polymorphisms did not show association with the AAM. Patients with severe IS form revealed delayed AAM than patients with mild IS form.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-383) contains supplementary material, which is available to authorized users.

Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer

Ethnic differences in patient genetics and breast cancer (BC) biology contribute to ethnic disparities in cancer presentation and patient outcome. We prospectively evaluated SNPs within phase I and phase II tamoxifen (TAM) metabolizing enzymes, and the estrogen receptor gene (ESR1), aiming to identify potential pharmacogenomic ethnicity patterns in an ER-positive BC cohort constituted of Hispanic and Non-Hispanic White (NHW) women in South Texas. Plasma concentrations of TAM/metabolites were measured using HPLC. CYP2C9, CYP2D6 and SULT1A1 genotypes were determined by DNA sequencing/Pyrosequencing technology. ESR1 PvuII and XbaI SNPs were genotyped using Applied Biosystems Taqman Allelic Discrimination Assay. Hispanics had higher levels of TAM, 4-hydroxytamoxifen, and endoxifen than NHWs. There was a higher prevalence of CYP2D6 EM within Hispanics than NHWs, which corresponded to higher endoxifen levels, but no differences were verified with regard to CYP2C9 and SULT1A1. We found a higher incidence of the wild type forms of the ESR1 in Hispanics than NHWs. The performance status, the disease stage at diagnosis, and the use of aromatase inhibitors might have overcome the overall favorable pharmacogenomics profile of Hispanics when compared to NHWs in relation to TAM therapy responsiveness. Our data strongly point to ethnical peculiarities related to pharmacogenomics and demographic features of TAM treated Hispanics and NHWs. In the era of pharmacogenomics and its ultimate goal of individualized, efficacious and safe therapy, cancer studies focused on the Hispanic population are warranted because this is the fastest growing major demographic group, and an understudied segment in the U.S.

Meta-analysis of associations of IL1 receptor antagonist and estrogen receptor gene polymorphisms with systemic lupus erythematosus susceptibility.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects a number of different organs and tissues. Interleukin-1 (IL1) and estrogen are considered potential elements in the pathology of SLE. Recently, the variable number of tandem repeats (VNTR) polymorphism in the IL1 receptor antagonist gene (IL1-RN) and PvuII (rs2234693) and XbaI (rs9340799) polymorphisms in the estrogen receptor 1 gene (ESR1) have been associated with a predisposition to SLE. However, the evidence for these associations is inconclusive. We therefore conducted a meta-analysis to validate the roles of these polymorphisms in SLE susceptibility. We searched four databases and identified a total of 17 eligible articles comprising 24 studies. The Newcastle-Ottawa quality assessment scale was used to assess the qualities of the selected studies. We assessed the strengths of the associations using odds ratios (ORs) with 95% confidence intervals (95% CIs). Regarding the IL-1RN VNTR, the 2 allele significantly increased SLE susceptibility (2 vs. L: OR = 1.34, 95% CI = 1.03–1.73, P = 0.03). The ESR1 PvuII CC/CT genotype was also associated with SLE susceptibility (CC/CT vs. TT: OR = 1.25, 95% CI = 1.06–1.47, P = 0.01), and the difference was especially pronounced among Asians (CC/CT vs. TT: OR = 1.33, 95% CI = 1.04–1.69, P = 0.02). No significant association between the ESR1 XbaI polymorphism and SLE susceptibility was observed in the overall analysis. However, a marginally significant association between the GG/GA genotype was found in individuals of Asian descent (GG/GA vs. AA: OR = 1.30, 95% CI = 1.01–1.67, P = 0.04). These results indicate that the IL1-RN VNTR 2 allele, ESR1 PvuII CC/CT genotype and ESR1 XbaI GG/GA genotype may increase SLE susceptibility, especially in Asian individuals.

Estrogen receptor α gene polymorphisms and risk of Alzheimer's disease: evidence from a meta-analysis.

ObjectiveHuman estrogen receptor α (ESR1), a member of the nuclear receptor superfamily of ligand-activated transcription factors, is one of the key mediators of hormonal response in estrogen-sensitive tissues. Accumulating evidence has demonstrated that two of the most widely studied single-nucleotide polymorphisms in ESR1 – PvuII (T/C, rs223493) and Xbal (A/G, rs9340799) – are possibly associated with Alzheimer’s disease (AD). However, individual study results are still controversial.Materials and methodsWe searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, and the Chinese National Knowledge Infrastructure databases for eligible studies assessing the association of ESR1 polymorphisms and AD risk (last search performed in November 2013). Thereafter, a meta-analysis of 13,192 subjects from 18 individual studies was conducted to evaluate the association between ESR1 polymorphisms and susceptibility to AD.ResultsThe results indicated that a significant association was found between the ESR1 PvuII polymorphism and AD risk in Caucasian populations (CC + CT versus TT, odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02–1.28, P=0.03; CT versus TT, OR 1.16, 95% CI 1.02–1.31, P=0.02), whereas no evidence of association was found in Asian populations. Nevertheless, we did not find any significant association between the ESR1 XbaI polymorphism and AD risk for any model in Caucasian and Asian populations (all P>0.05).ConclusionBased on this meta-analysis, we conclude that the ESR1 PvuII polymorphism might be a risk factor in AD development in Caucasian populations, not in Asian populations. Further confirmation is needed from better-designed and larger studies.

Meta-analysis of PvuII, XbaI variants in ESR1 gene and the risk of Alzheimer's disease: The regional European difference

The PvuII and XbaI polymorphisms of ESR1 gene have been reported in the Alzheimer's disease (AD) studies. However, whether these ESR1 genetic variants can contribute to the risk of AD remains controversial. Herein, we conducted a meta-analysis to clarify the association between ESR1 polymorphisms and the occurrence of AD. Articles were identified by systematic searches in PubMed, Google scholar and Wan Fang Med Online database. The combined odds ratios (OR) and 95% confidence intervals (CI) were calculated within different inherited models. Publication bias tests, subgroup analyses and sensitive analyses were also performed. Overall, the PvuII variant was negatively associated with AD in the Caucasian population (pp vs PP+Pp, OR 0.86, 95%CI (0.76, 0.96)). However, there was a poor association between XbaI polymorphism and AD in European populations. In particular, PvuII variant was found significantly associated with a decreased AD risk in South European samples (pp vs PP+Pp, OR 0.86, 95%CI (0.75, 0.98)). This meta-analysis indicated that regional European differences of ESR1 PvuII polymorphism in the association with the occurrence of AD, which need to be further identified, especially in South European countries.

Association of polymorphisms in estrogen receptors (ESR1 and ESR2) with male infertility: a meta-analysis and systematic review

Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different regions of ESR1 and ESR2 genes. However, results from published studies on the association between four well-characterized polymorphisms (PvuII, XbaI, RsaI, and AluI) in the gene of ERs (ESR1 and ESR2) and male infertility risk are inconclusive. To investigate the strength of relationship of PvuII and XbaI in ESR1 and RsaI and AluI in ESR2 with male infertility, we conducted a meta-analysis of 12 eligible studies with odds ratio (OR) and its corresponding 95% confidence intervals (95% CI). Overall, ESR1 PvuII and ESR2 RsaI polymorphisms were significantly associated with male infertility risk. The subgroup analyses by ethnicities demonstrated that in Asians, ESR1 PvuII, XbaI and ESR2 RsaI polymorphisms were significantly associated with a decreased infertility risk, while in Caucasians both ESR1 PvuII and ESR2 RsaI polymorphisms increased the susceptibility to male infertility. As for ESR2 AluI polymorphism, no significant association was detected in either overall analysis or subgroup analyses by ethnicities/genotyping methods. This meta-analysis suggested that polymorphisms in the genes of ERs (ESR1 and ESR2) may have differential roles in the predisposition to male infertility according to the different ethnic backgrounds. Further well-designed and unbiased studies with larger sample size and diverse ethnic backgrounds should be conducted to verify our findings.

Preliminary testing for endometriosis and gene polymorphisms

We read your review on the relation between endometriosis and ovarian cancer 1. Endometriosis is characterized by inflammation and invasion of endometrial cells into other tissues and organs. It is a serious condition associated with complications such as infertility, dysmenorrhea, and dyspareunia in females of reproductive age, and the pathophysiology of the disease occurrence and progression is unclear. An evaluation for endometriosis should be considered for adolescent female patients with chronic pelvic pain because early diagnosis and management are important to maintain quality of life and reduce the need for extensive surgical management 2. Your review is highly informative for gynecologists to follow up patients with endometriosis and investigate the condition. We believe that it is important for gynecologists to know that ovarian cancer is associated with endometriosis. However, identification of a biomarker of the relation between endometriosis and ovarian cancer is needed. Single-nucleotide polymorphisms are currently under investigation in terms of the prediction and prevention of many diseases. Endometriosis is known to be an estrogen-dependent disease. Single-nucleotide polymorphisms of the CYP17 GG and GA genotype, which is related to steroidogenic genes, are significantly increased in infertile females with endometriosis 3. We have reviewed the estrogen receptor (ER) gene polymorphisms associated with endometriosis 4. Polymorphism in PvuII of ERα is associated with an increased tendency for endometriosis in Europe, and polymorphism in XbaI of ERα is associated with a risk of occurrence in both Asia and Europe 4. We also investigated the relation between MUC4 and endometriosis. Epithelial surfaces secrete mucous components composed of mucin-glycosylated proteins. The MUC series has been investigated with other mucous secretory-related cancer markers. MUC1 is overexpressed in ovarian tumors and is present in endometriotic lesions 5. We preliminarily studied associations between patients with two types of functional cysts and two patients with endometriosis in the ER and MUC4 genes by PCR, restriction fragment length polymorphism, or DNA sequencing. The clinical characteristics of the two patients with functional cysts and two patients with endometriosis are shown in Table 1, which shows that patients with endometriosis had four mutant haplotypes in MUC4 (rs882605, intron 22 + 66, intron 23 + 45, and intron 23 + 47) and a double-mutant haplotype in ESR1 PvuII and ESR1 XbaI (figure available on request). We also found that MUC4 (introns 23 + 45 and introns 23 + 47), ESR PvuII, and XbaI may be associated with endometriosis. However, small case reports cannot confirm the effect of polymorphisms on the relation between endometriosis and functional cysts. We plan to investigate the effect of ESR and MUC4 (introns 23 + 45 and introns 23 + 47) on the relation between endometriosis and functional cysts. One report showed that the MUC4 polymorphism was related to endometriosis and infertility in a Taiwanese population 6. No other reports have described endometriosis in association with polymorphisms of both the MUC4 and ER genes. We believe that a study of concurrent MUC4 and ERα polymorphisms would provide useful information for the diagnosis and prevention of recurrence of endometriosis.

Estrogen receptor α gene PvuII polymorphism and coronary artery disease: a meta-analysis of 21 studies

The association between the estrogen receptor α gene (ESR1) PvuII polymorphism (c.454-397T>C) and coronary artery disease (CAD) is controversial. Thus, we conducted a meta-analysis to evaluate the relationship. Data were collected from 21 studies encompassing 9926 CAD patients and 16710 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the relationship between PvuII polymorphism and CAD. The polymorphism in control populations in all studies followed Hardy-Weinberg equilibrium. We found a significant association between ESR1 PvuII polymorphism and CAD risk in all subjects. When the data were stratified by region, a significant association between ESR1 PvuII polymorphism and CAD risk was observed in Asian populations but not in Western populations. The current study suggests that ESR1 PvuII polymorphism has an important role in CAD susceptibility.

ESR1 and FSHR Gene Polymorphisms Influence Ovarian Response to FSH in Poor Responder Women with Normal FSH Levels

In COS (Controlled Ovarian Stimulation), individual response are highly variable. A number of studies have evaluated the ovarian response to FSH in women most often aged over 35 years and with high FSH level. But we see also a poor response to ovarian stimulation in young women (<32 years) with normal FSH levels.The aim of this study was to evaluate the relationship between FSHR and ESR1 gene polymorphism in this young women population. For 70 patients, the FSHR p.Ala307Thr (rs6165) and p.Ser680Asn (rs6166) single-nucleotide polymorphisms (SNPs), the ESR1 PvuII T/C (rs2234693) SNP, and the (TA)n microsatellite polymorphism were studied alone or in combination. We found that the frequency of the p.307[Ala;Ala] FHSR genotype was 3-fold higher in poor responders (PRs) to COS (Controlled Ovarian Stimulation) than in good responders (GRs).The frequency of ESR1 polymorphism was not correlated with the FSH response. In the combined analysis of FSHR and ESR, ESR1 polymorphism seems to improve the efficiency of prediction of the FSHR polymorphism. The more specifics genotypes were FSHR307[Ala;Ala]/ ESR1 (TA)[>16; 16; 16;>16] for GRs. Our study show the involvement of ESR1 and FSHR polymorphisms and the multi-genic spectrum of ovarian response to gonadotropin in women with normal gonadotropin levels. Moreover, the poor response to FSH linked to the 307GG genotype was not associated with an increase in plasma FSH.

Association between Estrogen Receptor α Gene (ESR1) PvuII (C/T) and XbaI (A/G) Polymorphisms and Hip Fracture Risk: Evidence from a Meta-Analysis

Background and ObjectiveGenetic factors are important in the pathogenesis of fractures. Notably, estrogen receptor α (ESR1) has been suggested as a possible candidate gene for hip fractures; however, published studies of ESR1 gene polymorphisms have been hampered by small sample sizes and inconclusive or ambiguous results. The aim of this meta-analysis is to investigate the associations between two novel common ESR1 polymorphisms (intron 1 polymorphisms PvuII-rs2234693: C>T and XbaI-rs9340799: A>G) and hip fracture.MethodsCrude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the association.ResultsFive case-control and three cohort studies were assessed, including a total of 1,838 hip fracture cases and 14,972 healthy controls. This meta-analysis revealed that the PvuII T allele is a highly significant risk factor for hip fracture susceptibility, with an effect magnitude similar in male and pre-menopausal and post-menopausal female patients. In stratified analysis based on ethnicity, the PvuII T allele remained significantly correlated with increased risk of hip fracture in Caucasian populations; this correlation, however, was not found in Asian populations. Unlike the PvuII polymorphism, we did not find significant differences in the XbaI (A>G) polymorphism allele or genotype distributions of hip fracture patients and controls. We also found no obvious association between the XbaI polymorphism and hip fracture in any of the racial or gender subgroups.ConclusionOur findings show that the ESR1 PvuII T allele may increase the risk of hip fracture and that the XbaI polymorphism is not associated with hip fracture.