Estrogen Receptor Beta Gene Polymorphisms Research Articles

Status of Estrogen Receptor Beta Gene Polymorphisms rs1256049 and rs4986938 in a cohort of South Indian women with Primary ovarian insufficiency

The current study is aimed to investigate the role of estrogen receptor beta gene polymorphisms for causation of Primary Ovarian insufficiency (POI) in south Indian women. Primary Ovarian insufficiency (POI) is a menstrual disorder presenting with Primary and secondary amenorrhea, decreased estradiol levels and increased gonadotrophin levels. Most cases of POI remain unresolved even after exhaustive investigations and is a significant cause of infertility in women in the reproductive age. In this study a total of 276 subjects, of which 138 POI patients and 138 controls were analysed for biochemical profiles of FSH, LH and Estradiol. Genotypic frequencies were calculated for different models of the SNP rs1256049 and rs4986938 in the Estrogen receptor Beta gene by PCR-RFLP (Restriction length polymorphism) analysis. Statistically, significant relation is found for FSH, LH and Estradiol profiles of a different group of Premature ovarian insufficiency and controls (p<0.0001). Genotypic frequencies between patients and controls were compared, and strength of the interdependence of genotypes and POI is confirmed by the odds ratio and 95% confidence intervals. Incidence of 1082 G>A (rs1256049) polymorphisms and 1730 G>A (rs4986938) were not significantly different in both patient and control group (P=0.21 and P=0.4). The presence of 1082 G>A (rs1256049) polymorphisms and 1730 G>A (rs4986938) is not associated with causation of Premature ovarian insufficiency in south Indian women.

Status of Estrogen Receptor Beta Gene Polymorphisms rs1256049 and rs4986938 in a cohort of South Indian women with Primary ovarian insufficiency

The current study is aimed to investigate the role of estrogen receptor beta gene polymorphisms for causation of Primary Ovarian insufficiency (POI) in south Indian women. Primary Ovarian insufficiency (POI) is a menstrual disorder presenting with Primary and secondary amenorrhea, decreased estradiol levels and increased gonadotrophin levels. Most cases of POI remain unresolved even after exhaustive investigations and is a significant cause of infertility in women in the reproductive age. In this study a total of 276 subjects, of which 138 POI patients and 138 controls were analysed for biochemical profiles of FSH, LH and Estradiol. Genotypic frequencies were calculated for different models of the SNP rs1256049 and rs4986938 in the Estrogen receptor Beta gene by PCR-RFLP (Restriction length polymorphism) analysis. Statistically, significant relation is found for FSH, LH and Estradiol profiles of a different group of Premature ovarian insufficiency and controls (p A (rs1256049) polymorphisms and 1730 G>A (rs4986938) were not significantly different in both patient and control group (P=0.21 and P=0.4). The presence of 1082 G>A (rs1256049) polymorphisms and 1730 G>A (rs4986938) is not associated with causation of Premature ovarian insufficiency in south Indian women.

Estrogen receptor beta gene polymorphisms and risk of recurrent pregnancy loss: a case–control study

Estrogen might play a key role in the maintenance of pregnancy. We investigated the role of the ER-β gene +1730 G/A, +1082 G/A, and CA repeat polymorphisms in Korean patients with recurrent pregnancy loss (RPL). Genotyping was performed using the TaqMan assay in 305 patients with at least two unexplained consecutive spontaneous miscarriages before 20 weeks of gestation and 299 controls. The genotype distributions of the ER-β gene +1082 G/A and +1730 G/A polymorphisms in the RPL group did not differ from those in the control group. When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages, there were also no differences in the genotype distribution between this subgroup and controls. The number of CA repeats was distributed from 13 to 28 with two large peaks at 18 and 23 in patients with RPL and controls. Using the two major peaks as cut-offs, the allele distributions were compared between patients and controls. However, the distribution of ER-β gene CA repeats did not differ between women with recurrent miscarriage and controls. Findings of the current study suggest that the ER-β gene polymorphisms are not major determinants of the development of RPL in Korean women.

Estrogen Receptor-beta Gene Polymorphism Affects Carotid Arterial Elasticity and Wall Mass in Japanese Women

Estrogen Receptor-beta Gene Polymorphism Affects Carotid Arterial Elasticity and Wall Mass in Japanese Women

Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms

The role of estrogen receptor beta (ERβ) in breast cancer has been investigated since its identification in 1996. Studies based on protein expression have indicated that ERβ is a favorable prognostic marker. Further, ERβ expression is lower in obese breast cancer patients. Fewer studies have focused on the prognostic impact of ERβ polymorphisms. Therefore, we analyzed the associations between four previously identified haplotype tagging single nucleotide polymorphisms (htSNPs), associated haplo- and diplotypes, and breast cancer-free survival according to body constitution. The patient cohort included 634 women from the prospective breast cancer and blood study (BC Blood study, Sweden) with a median follow-up of 4.92years. Four htSNPs (i.e., rs4986938, rs1256049, rs1256031, rs3020450) in the ESR2 gene and the correlating haplo- and diplotypes were analyzed and correlated to selected patient and tumor characteristics and to disease-free survival, including stratification for BMI. Based on the four htSNPs, seven haplotypes and eight diplotypes were identified. The patient and tumor characteristics were well-balanced across all geno- and haplotypes. Disease-free survival differed according to rs4986938 and rs1256031 (Log-Rank P=0.045 and P=0.041, respectively) and the number of haplotype copies of the wildtype CCGC and TCAC (Log-Rank P=0.027 and P=0.038, respectively). In the survival analyses stratified for BMI, significant survival differences between alleles were observed among overweight women (rs4986938 and rs1256031 with Log-Rank P=0.001 and P=0.001, respectively). The BMI-stratified survival analyses based on haplotypes showed shorter disease-free survival for overweight women with null copies of CCGC (Log-Rank P=0.001) and for overweight women with any TCAC copy (Log-Rank P<0.0001). Markedly impaired disease-free survival was found for genotypes in two out of four ESR2 htSNPs and for two haplotypes. ESR2 polymorphisms seem to divide patients into good and poor survivors based on BMI, stressing the need of taking host factors into consideration in the evaluation of prognostic markers.

Association between estrogen receptor beta gene polymorphisms in Chinese Uygur patients and intrahepatic cholestasis of pregnancy

To assess the association between estrogen receptor beta gene (ERβ) polymorphisms and intrahepatic cholestasis of pregnancy (ICP) in Chinese Uygur patients. A total of 105 ICP patients and 105 healthy controls were recruited from April 2008 to April 2011. Polymorphisms of rs1256049 (Rsa I) and rs4986938 (Alu I) in ERβ gene were analyzed with PCR-restriction fragment length polymorphism (RFLP) method. The frequencies of R allele were, respectively, 35.71% and 50.95% in ICP patients and controls. Odds ratio (OR) was 0.535 [95% confidence intervals (CI) = 0.3619-0.7910, P< 0.01]. Frequencies of A allele were, respectively, 21.43% and 10.95% in the patient and control groups. OR was 2.2174 (95% CI = 1.2866-3.8215, P<0.05). ERβ gene polymorphisms are associated with ICP. R allele may confer a protective effect, whilst A allele may be a risk factor.

Estrogen Receptor-Beta Gene Polymorphism in women with Breast Cancer at the Imam Khomeini Hospital Complex, Iran

ER-alpha and ER-beta genes have been proven to play a significant role in breast cancer. Epidemiologic studies have revealed that age-incidence patterns of breast cancer in Middle East differ from those in the Western countries. Two selected coding regions in the ER-β gene (exons 3 and 7) were scanned in Iranian women with breast cancer (150) and in healthy individuals (147). PCR single-strand conformation polymorphism was performed. A site of silent single nucleotide polymorphism was found only on exon 7. The SNP was found only in breast cancer patients (5.7%) (χ2 = 17.122, P = 0.01). Codon 392 (C1176G) of allele 1 was found to have direct association with the occurrence of lymph node metastasis. Our data suggest that ER-β polymorphism in exon 7 codon 392 (C1176G) is correlated with various aspects of breast cancer and lymph node metastasis in our group of patients.

Estrogen Receptor Beta Gene Polymorphisms is Correlated With Bone Mineral Density, But Not Osteoporotic Fracture in Postmenopausal Women

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) in the estrogen receptor beta (ESR2) gene and bone mineral density (BMD) and osteoporotic fracture in postmenopausal women. Methods: Spine and hip BMD as well as fracture history were investigated in 140 postmenopausal Chinese women. Genotyping was performed for 3 SNPs of ESR2 gene, Van91| and Rsa| in exon 5, and AluI in exon 8. For each SNP, subjects were divided into 2 groups: the “carrier group” including individuals with at least 1 allele bearing the restriction site and the “wild-type group” including the rest of the subjects. Results: Only VV genotype was observed for the Van91| locus. The distribution of RsaI genotypes was 81.43% for RR, 17.14% for Rr, 1.43% for rr, and of AluI genotypes was 87.86% for AA and 12.14% for Aa, and aa was absent. Spine BMD differed significantly in the 2 groups of RsaI SNP after adjusting for confounding variables (P = 0.0042), while hip BMD differed significantly in the 2 groups of AluI SNP after adjustment (P < 0.01). No correlation was observed between osteoporotic fracture and either RsaI or AluI SNP (P > 0.05). Conclusions: The RsaI and AluI SNPs of ESR2 gene may influence BMD variation, but does not appear to correlate with the risk of osteoporotic fracture in postmenopausal women.

Association between RsaI and AluI polymorphism in the estrogen receptor beta gene and primary hepatocellular carcinoma.

To investigate whether there is a association between estrogen receptor beta (ERb) gene polymorphism and primary hepatocellular carcinoma (HCC). 100 primary HCC patients and 100 controls from southwestern China were recruited in this study. The polymorphism of RsaI and AluI in ERb gene was analyzed by PCR- restriction fragment length polymorphism (RFLP). R allelic frequency was 35.0% and 51.0% in HCC patients and in control group, respectively, odds ratio (OR) was 0.517 [95% confidence intervals (CI) = 0.346-0.773], P less than 0.01. A allelic frequency was 20.5% and 11.0% in HCC patients and in control group, respectively, OR was 2.086 (95% CI = 1.191-3.654), P less than 0.01. Gene frequency of RsaI and AluI in the two groups was distributed with polymorphism. ERb gene polymorphism is associated with primary liver cancer. R allele may be the guard factor, and A allele may be its risk factor.

Association between estrogen receptor beta gene polymorphisms and Parkinson disease

To investigate the association between two estrogen receptor (ER) beta gene polymorphisms and Parkinson disease (PD) as well as Parkinson disease with dementia (PDD) in Chinese people. Peripheral blood samples were collected from 115 PD patients (including 26 PDD cases), 56 males and 55 females, aged 64 +/- 10, and 116 sex and age-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to analyze the polymorphism of the fifth exon RsaI and the eighth exon AluI of ERbeta gene. Te relationship between each genotype or allele frequencies and PD/PDD was analyzed using chi-square test. There was no difference in the polymorphism of ERbeta genes AluI and Rsa I between the PD group and control group and between the PDD group and control group (all P > 0.05). Genetic variations from AluI and RsaI digestion in ERbeta gene do not affect the risk of PD and PDD.

Association of estrogen receptor beta gene polymorphism with menopausal symptoms

Association of estrogen receptor beta gene polymorphism with menopausal symptoms

Correlation of estrogen receptor beta gene polymorphisms with spinal bone mineral density in peri- and post-menopausal Greek women

Estrogens play a significant role in bone physiology. Their action is mainly exerted through their receptors. Estrogen receptor alpha (ERα) plays a major role in bone homeostasis and there is evidence suggesting that estrogen receptor beta (ERβ) has also an effect on BMD. We investigated the possible effect of two ERβ gene polymorphisms on spinal bone mineral density (BMD) and metabolic bone markers in Greek women. Spine BMD as well as biochemical bone markers were measured in 147 healthy peri- and post-menopausal women [mean age (S.D.) 54 (7.9) years]. Genotyping was performed for two restriction fragment length polymorphisms (RFLPs) of ERβ gene, RsaI in exon 5 and AluI in exon 8. For each polymorphism studied the cohort was divided into two groups: the “wild-type” group (RR and AA, respectively) and the “carrier” group including subjects with at least one allele with the restriction site (Rr&rr and Aa&aa, respectively). The distribution of RsaI genotypes was RR: 91.2% ( n = 134), Rr: 8.2% ( n = 12), and rr: 0.6% ( n = 1) and of AluI genotypes AA: 36.7% ( n = 54), Aa: 57.2% ( n = 84), and aa: 6.1% ( n = 9). No linkage disequilibrium was found between the two polymorphic sites studied. Spine BMD did not differ significantly in the two groups of either polymorphism, after adjusting for age, weight, height, and years since menopause [mean BMD (S.D.) for RR 0.841 (0.17) g/cm 2 versus Rr&rr 0.798 (0.13) g/cm 2, p = 0.25, and mean BMD (S.D.) for AA 0.828 (0.16) g/cm 2 versus Aa&aa 0.848 (0.17) g/cm 2, p = 0.32]. No significant differences were noted in metabolic bone markers except for a marginal difference of RR versus Rr/rr in urinary hydroxyproline/creatinine ratio [median (IQR) 3.88 (6.04) μmol/mmol in RR versus 8.2 (4.32) μmol/mmol in Rr/rr, p = 0.05]. Furthermore, no interaction between the two polymorphisms on BMD was found. In conclusion, in a Greek female post-menopausal population, the two ERβ gene polymorphisms were not associated with BMD, or metabolic bone markers.

Association of estrogen receptor beta gene polymorphisms with bulimic disease in women.

In this study, we explored the potential association between estrogen receptor beta (ERbeta) and disease in a group of bulimic women. Eating disorders are much more common in females than in males, suggesting a possible role for female sex hormone signalling in the pathogenesis of these diseases. Furthermore, estrogen has been implicated in appetite regulation. The occurrence of menstrual disturbances is also increased in bulimic women. We studied 76 bulimic women and 60 controls, and found an association between two common polymorphisms in the ERbeta gene with disease in this group of bulimic women. More detailed characterisation of the ERbeta gene identified a novel variant changing the primary structure of ERbeta protein in one bulimic patient. An initial functional characterization of this variant did not reveal any differences compared to the wild-type protein. Our findings point towards a possible role of ERbeta and/or neighboring genes in the etiology of disease in bulimic patients.