Estrogen Receptor Polymorphisms Research Articles

Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment.

Vascular cognitive impairment (VCI) is a term that encompasses a continuum of cognitive disorders with cerebrovascular pathology contribution, ranging from mild cognitive impairment to vascular dementia (VaD). VCI and VaD, thus, represent an interesting intersection between cardiovascular disease and neurodegenerative disorders such as Alzheimer's disease (AD) and a rising area of research in recent years. Although VCI and VaD research has identified various causes and explanations for disease development, many aspects remain unclear, particularly sex differences in VCI (e.g., epidemiology), unlike those available for cardiovascular disease and AD. Despite limited information in the literature, several studies have observed an association of estrogen receptor (ER) polymorphisms and VaD. If further explored, this association could provide valuable insights for novel therapeutic approaches. This review aims to provide a brief epidemiological overview and subsequent discussion exploring concepts of brain aging and involvement of estrogen receptors in potential mechanisms of VCI/VaD pathogenesis and treatment development.

Alpha estrogen receptor polymorphisms and their association with breast density.

In the development of breast cancer (BC), estrogen exposure and the increase in breast density (BD) are two determinant factors for BC risk. To identify the relationship between the XbaI and PvuII polymorphisms in the estrogen receptor (ER-alpha) with BD. Cross-sectional study which included 225 women, aged 40-65 years, without evident cancer data, who underwent routine mammography for early BC diagnosis in a radiology department. Two groups were formed: women with increased and with normal BD. Participants were genotyped for the XbaI and PvuII polymorphisms. 19.1% had normal weight, 37.7% overweight, and 43.2% were obese women. In relation to high-risk patterns, 105 women had increased BD and 120 had normal BD (53.3%). The frequency of women with increased BD was also lower in postmenopausal women. Regarding the type of BD, there was no statistically significant difference between frequencies of PvuII and XbaI genotypes. Logistic regression showed that only age and body mass index (BMI) were associated with BD. PvuII and XbaI ER-alpha genotypes were similar among women with dense and non-dense breasts; differently, other factors were associated with BD (age, BMI and menopausal status). Therefore, emphasis should be placed on clinical practice in the relationship between BMI and BD.

Interaction estrogen receptor polymorphism associates with psychosocial stress on menopausal women

This research aimed to evaluate the interaction between polymorphisms of ERα & ERβ and associated with psychosocial stress on menopausal women. It was a cross-sectional study, subject were 102 women aged 40-70 years who meet the inclusion criteria at the Obstetrics and Gynecology Education Hospital of Hasanuddin who agreed on filling questioner which have been determined. Then proceed with blood taking for the ERα and ERβ receptor polymorphisms. Genomic DNA was isolated from 1mL of EDTA anticoagulation edge blood sample using a salting-out procedure and examined interaction of polymorphisms receptors ERα and ERβ. The data were statistically analyzed using the chi-square test with p-value<0.05. This research showed that subjects who experienced psychosocial stress have the most ERα Pvull heterozygous Pp polymorphism, ERα Xbal homozygous recessive xx, and homozygous dominant ERβ AA. There is ERβ polymorphism relationship with the occurrence of psychosocial stress in menopausal women. But there is no relationship between polymorphisms ERα Pvull, ERα Xbal, as well as the interaction between polymorphisms of ERα and ERβ with the occurrence of psychosocial stress in menopausal women. ERβ polymorphism relationship the occurrence of psychosocial stress in menopausal women.

The association of estrogen-signaling pathways and susceptibility to open-angle glaucoma

BackgroundGlaucoma is a complex multivariate disorder characterized by retinal ganglion cell (RGC) loss and optic nerve degeneration. Evidence suggests the role of estradiol (E2) and the etiology of glaucoma. Therefore, this present study evaluates the association between estrogen-signaling pathways and the risk of open-angle glaucoma (OAG).ResultsMeta-analysis was performed from available studies that investigated intraocular pressure (IOP) in patients treated with or without hormone replacement therapy (HRT) and studies that evaluated the associations between estrogen receptor (ER) polymorphisms and the risk of OAG. The pooled result showed that HRT had a positive effect in lowering IOP. Moreover, ERβ polymorphisms showed a significant association with the risk of OAG.ConclusionThis report supports the notion that estrogen-signaling pathways play a pivotal role in the development of OAG.

Polymorphisms of Estrogen Receptor-α and Estrogen Receptor-β Genes and its Expression in Endometriosis

Objectives Endometriosis is a common gynecological disorder, characterized by the presence of endometrial-like tissue in the extrauterine location. The increasing estradiol concentration can influence endometriosis risk and estrogen receptor (ER) activity. Polymorphism in ER causes gene expression alteration and influences hormone-receptor interaction. This research aims to determine ER genetic polymorphisms in endometriosis pathogenesis. Materials and methods This study was performed on case-control polymorphisms, which compared 83 women with endometriosis and 76 women without endometriosis. However, the samples used for ER gene expression analysis and estrogen level measurement were obtained from 18 women with endometriosis and 18 women without endometriosis. Polymerase chain reaction-restriction fragment length polymorphism was used to determine ER genetic polymorphisms. Chi-square, Mann-Whitney test, Spearman's correlation (p), t-independent, and two-tailed tests were used to analyze the data. Results Association between the allele ERα rs9340799 A/G and endometriosis was significantly different (p=0.012), whereas rs2234693 T/C polymorphism showed no association with endometriosis. The correlation between the genotype frequencies of allele ERβ rs4986938 G/A and endometriosis was found significantly different (p=0.015; p=0.034). Conclusion Estradiol level and ERβ expression increases, polymorphism genotypes and alleles of ERβ rs4986938 G/A gene and allele frequency of ERα rs9340799 A/G gene have roles in endometriosis.

PvuII and XbaI in Estrogen Receptor 1 (ESR1) Polymorphisms and Susceptibility to Endometriosis Risk.

Studies have shown that variants in PvuII and XbaI loci are associated with the occurrence and progression of endometriosis (EM), while the results were in great debate. A systematic review and meta-analysis were conducted to evaluate the role of PvuII and XbaI polymor-phisms in estrogen receptors (ESR1). The primary sources of the reviewed studies through December 2018, with restriction on the language of English and Chinese, were Pubmed and Embase and CNKI. The pooled odds ratio 95% confidence intervals (CIs) were calculated to evaluate the associations of Pvull and Xbal polymorphisms with the risk of EM by using the STATA 14.0 software. A total of 18 studies with 4,975 patients, 2,222 in the case group, 2,753 in the control group, were in the final analysis. Overall pooled outcomes did not indicate significant correlations between the ESR1 Pvull/Xbal polymorphisms and the EM development. In subgroup analysis, PvuII was associated with endometriosis only for stage I - III and only under a recessive model (OR = 1.61, 95% CI: 1.03 to 2.07; p = 0.03). Xbal was associated with endometriosis only for the non-PCR-RFLP genotype method and also only under a recessive model (OR = 2.10, 95% CI: 1.21 to 4.47; p = 0.04). This present meta-analysis reported that polymorphisms of PvuII or Xbal were not related to the susceptibility to EM except for a slight association of stage I-III endometriosis and non-PCR-RFLP under recessive model. Future, well-designed large studies are eagerly awaited to confirm our conclusions.

Effects of vitamin D and estrogen receptor polymorphisms on bone mineral density in adolescents with anorexia nervosa.

Background Anorexia nervosa (AN) is a serious eating disorder that is associated with decreased bone mineral density (BMD) and greater lifetime risk for fractures. The aim of this study was to determine the correlation between BMD and genetic polymorphisms in AN. Methods This case-control study analyzed vitamin D receptor (VDR) (VDRBsml, VDRFokl) and estrogen receptor (ESR) (ESR1Xbal, ESR1Pvull) polymorphisms in 45 adolescents diagnosed with AN and 46 age-matched healthy controls. BMD values of the AN group were classified as low or normal, and polymorphisms were compared between cases and controls. The effects of body mass index (BMI), duration of disease and amenorrhea on BMD were also evaluated. Results In girls with AN, a positive effect of the bb genotype of VDRBsmI polymorphism on femur Z-scores (p = 0.103) and of the Ff genotype of VDRFokI polymorphism on vertebra Z-scores (p = 0.097) was observed. In boys with AN, a positive effect of the Ff genotype of VDRFokI polymorphism on vertebra BMD (g/cm2) was detected (p = 0.061). No association was detected between ESR polymorphisms. An inverse relationship was observed between BMD and duration of illness and amenorrhea. A direct relationship was detected between BMD and BMI. Conclusions Specific VDR gene polymorphism genotypes may have positive effects on BMD in patients with AN. Additionally, the lack of association between ESR gene polymorphisms on BMD could be attributed to the low estrogen status of the patient.

Relationship of estrogen beta (ERβ) receptor genes polymorphism with epithelial ovarian cancer

Ovarian cancer is the leading cause of death among all uterine diseases. Ovarian cancer is affected by exogenous and endogenous estrogen factors. Beta estrogen receptors are predominant estrogen receptors in the normal ovary. Polymorphisms in the beta estrogen receptor gene (ERβ) can affect the risk of epithelial ovarian cancer through regulation of cell proliferation and apoptosis. The purpose of this study was to determine the relationship of beta estrogen receptor gene polymorphism (ERβ) with epithelial ovarian cancer incidence. Method: a case-control study, there were 60 samples. A single nucleotide polymorphism in the beta estrogen receptor (RsaI/rs1256049) is selected. Genotyping using PCR-RFLP. Data were analyzed by Chi-square, considered significant if the p-value is less than 0.05. Results: there is no significant difference in the characteristics of respondents. Genotypic frequency in the case group was 56.7% GG, 43.3% GA/AA and control group was 23.2% GG, 76.7% GA/AA. The frequency of alleles in the case group was 78.3% G, 21.7% A and control which was 50% G, 50% A allele. ERβ polymorphism is associated with epithelial ovarian cancer (p 0.018). Allele A in RsaI was associated with epithelial ovarian cancer (p 0.002). Polymorphism of the beta estrogen receptor gene associated with epithelial ovarian cancer.

Evaluation of the epidemiological and prognosis significance of ESR2 rs3020450 polymorphism in ovarian cancer

AimTo investigate the correlation between the polymorphism of estrogen receptor β gene (ESR2) rs3020450 and cancer susceptibility, and explore the epidemiological significance and the effect of ESR2 expression levels on the prognosis of ovarian cancer. MethodsBased on meta-analysis the association between ESR2 rs3020450 polymorphism and cancer susceptibility was estimated and a case-control design was used to verify this result in ovarian cancer. The epidemiological effect of ESR2 rs3020450 polymorphism was assessed by attributable risk percentage (ARP) and population attributable risk percentage (PARP). Kaplan Meier plotters were used to evaluate overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients and GEPIA for the differential expression of ESR2 levels in ovarian cancer and adjacent normal tissues. ResultsThe pooled analysis indicated no significant correlation between the ESR2 rs3020450 polymorphism and the cancer susceptibility. In the stratified analysis by cancer types, significantly decreased risk was found in ovarian cancer (AG vs GG: OR = 0.73, 95%CI: 0.53–0.97, P = 0.03). Unconditional logistic regression results of case-control study in ovarian cancer observed significant differences in all comparisons (AG vs GG: OR = 0.81, 95%CI: 0.62–0.98, P = 0.04; AA vs GG: OR = 0.63, 95%CI: 0.42–0.92, P = 0.01 and AG + AA vs GG: OR = 0.73, 95%CI: 0.53–0.96, P < 0.001). Based on meta-analysis and case-control pooled results, ARP and PARP were evaluated respectively in allele (21.95% and7.97%), heterozygote (36.99% and 12.11%) and dominant model (36.84% and 12.97%) of rs3020450 polymorphism in ovarian cancer. The expression levels of ESR2 in normal tissues was significantly higher than that in cancer tissues (OV, Median, 4.7:0.21), and significant correlations were observed between high ESR2 expression levels and long OS (HR = 0.80, 95%CI: 0.70–0.92, P = 0.002) and PFS (HR = 0.767, 95%Cl: 0.67–0.88, P < 0.001). ConclusionOur results indicated that ESR2 rs3020450 polymorphism was associated with ovarian cancer risk from epidemiological perspective, and high ESR2 expression levels was associated with long survival in patients with ovarian cancer.

Impact of orthognathic surgery in anxiety levels: clinical and genetic study

Background: Orthognathic surgery (OS) is a procedure for dentofacial deformities correction that leads people to change the perception of anxiety. Single nucleotide polymorphisms (SNP) in estrogen receptors are associated with anxiety.

SUN-041 Estrogen Pharmacogenetics in Patients with Turner Syndrome

Background: Turner syndrome (TS) is a disorder characterized by complete or partial absence of the second sexual chromosome and the most commonly found abnormalities are short stature and gonadal failure. Most TS patients need estrogen replacement but individual outcomes on uterine volume, breast development and vertebral bone density are highly variable. To our knowledge, the impact of polymorphisms in estrogen receptor 1 (ESR1) over the variability in the development of secondary sexual characteristics and in adult height has not yet been evaluated in TS patients. Objective: To investigate the association among five ESR1 polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) and breast development, uterine volume, vertebral bone density, FSH and LH levels and adult height in TS patients. Methods: We selected 80 TS patients receiving adult estrogen dose for a minimum period of one year. Patients who had spontaneous complete pubertal development or who have Y chromosome material in karyotype were excluded from analysis. They were submitted to clinical and laboratory evaluation, pelvic ultrasound, bone densitometry and genotyping of the five chosen ESR1 polymorphisms through real time PCR. These polymorphisms were selected through active search in Pubmed and in GWAS catalogs, based on the following criteria: recurrence in studies, being Tag-single nucleotide polymorphisms (Tag-SNPs) or having a minor allele frequency (MAF) which allowed the present study with the available sample. Results: 61% of patients had 45,X karyotype and their mean target height was 158.9cm. 82% of them were treated with rhGH for 5 years on average and they reached a mean adult height of 149cm. Their average age of puberty onset was 14.4 years old and 10% of them had spontaneous thelarche. Their mean uterine volume was 30.1cc but ranged from 5.9 to 83cc. 91% attained adult breast development (Tanner 5) and 93% had normal vertebral bone mass after correction for height (by using the online calculator from University of Washington: courses.washington.edu/bonephys). Only 15% had FSH and/or LH lower than 10 IU/L in two or more measurements. Considering the ESR1 polymorphisms, all of them were in Hardy-Weinberg equilibrium. Statistical analysis with multiple linear regression showed that none of the studied polymorphisms was able to predict any of the above estrogen therapy outcomes in an isolated manner. Conclusion: We could not find a relationship among the studied ESR1 polymorphisms and estrogen therapy outcomes in patients with TS. However, the high variability in estrogen replacement results suggests that genetic variants play an important role. Other efforts to identify polymorphisms associated to estrogen outcomes may allow for individualization of treatment in TS.

Clinical Importance of Estrogen Receptor 1 (ESR1) Gene Polymorphisms and Their Expression Patterns in Coronary Artery Disease Patients: A Study from India.

The influence of Estrogen Receptor 1 (ESR1) gene -397T>C (PvuII) and -351A>G (XbaI) polymorphisms on the risk of development of coronary artery disease (CAD) in the north Indian population was analysed. We hypothesized that ESR1 gene polymorphisms may influence the susceptibility to CAD through variation in Estrogen Receptor α (ERα) expression. To assess this concept, we evaluated ERα mRNA expression in blood plasma of CAD patients. The study included hundred CAD patients who showed presence of greater than 50% luminal stenosis in at least one major coronary artery in angiography along with hundred age and sex matched healthy controls. The ESR1 polymorphisms were investigated by PCR-RFLP. Quantitative Real Time PCR was carried out for the measurement of ERα mRNA expression. The results showed that genotypic frequencies of ESR1 -397T>C and -351A>G gene polymorphisms were significantly higher in CAD patients than control subjects (p < 0.0001). A significantly increased CAD risk was also found in dominant and codominant inheritance model for both of the SNPs. In gender based analysis these findings were replicated only in male subgroup. In case of -397T>C polymorphism, the ERα mRNA expression was highest in CAD patients with wild type homozygous TT genotype (2-∆ct = 0.28). A mutant 'C' allele, dose dependent, significant decrease in trend in ERα mRNA expression was observed, with lowest expression in mutant homozygous CC genotype (2-∆ct = 0.09), and intermediate expression level in heterozygous TC genotype (2-∆ct = 0.14) subgroups of CAD patients. In conclusion, this study demonstrates a significantly heightened risk of CAD associated with the inheritance of mutant genotypes of ESR1 -397T>C and -351A>G gene polymorphisms, in the north Indian population. This is the first report of a lowered ERα mRNA expression in conjunction with the presence of mutant 'C' allele of ESR1 -397T>C polymorphism with consequent increased CAD susceptibility.

Association between estrogen receptor 1 (ESR1) and leukemia inhibitory factor (LIF) polymorphisms can help in the prediction of recurrent implantation failure

To investigate an association between polymorphisms related to the implantation process that together could help in the prediction of recurrent implantation failure (RIF). Cohort study. Private fertility center and reproductive genetics laboratory. Forty-four women presenting RIF, who were included in study group (RIF group), and two control groups, one with 63 women who were attended at our service and became pregnant after the first IVF/intracytoplasmic sperm injection attempt (control group I) and other with 65 fertile women who had at least two children without any treatment and no history of miscarriage (control group II). None. Genotyping was performed in the intron region of TP63, VEGFA, MMP2, ESR1, and ESR2 genes and in the 3' untranslated region of the LIF gene on genomic DNA using real-time polymerase chain reaction. The presence of ESR1/AA (rs12199722) and LIF/GT (rs929271) genotypes was more frequent in the RIF group, leading to a 7.9-fold increase in the chance of women presenting with RIF when compared with women who became pregnant on their first cycle of IVF/intracytoplasmic sperm injection and a 2.8-fold increase when compared with women who became pregnant without treatment. The association between ESR1 and LIF polymorphisms can help in the prediction of RIF.

Evaluation of genetic polymorphism in estrogen receptor ? gene as breast cancer risk.

Breast cancer is very common cancer worldwide. Estrogen is one of the most important steroid hormones which play an important role in breast cancer. The aim of this study was to evaluate frequency distribution of ER-α gene SNPs in breast cancer patients and controls to find out any association with breast cancer risk. In the present study, two hundred breast cancer patients and one hundred age matched controls were taken to study breast cancer risk factors. The odd ratio (ORs) at 95% confidence interval (CIs) was computed to study significance of risk factor on menopausal status. Contribution of ESR1 gene in breast cancer was examined that allele frequency showed non-significant difference among patients and control group for rs138724640 and rs373404617 (p=0.4015 and p=0.8422 respectively). Odd ratio analysis showed that SNP rs2234693 and rs9340799 located on intron 1 were associated with breast cancer (p=0.0111, 0.025 respectively). SNP rs2077647 located on exon 3 showed only borderline significance (p=0.0777). C allele was found to be more prevalent in both patients and control group of rs138724640 and rs2234693. ‘A’ allele was more prevalent in breast cancer patients and controls of rs9340799 and in controls of rs373404617. The frequency of G allele was found to be more in breast cancer patients of rs373404617. In cases of SNP rs2077647, T allele was more frequent in both breast cancer patients and control group. Present study results suggest the difference of genotype distribution of ESR1 SNPs between breast cancer patients and controls; hence establish the association with breast cancer risk. Further validation studies are required on additional ESR1 SNPs to study the breast cancer risk using larger cohort.

Association between ESR1 polymorphisms and second to fourth digit ratio in school-aged children in the Hokkaido Study

The ratio of the lengths of the 2nd and 4th digits (2D:4D) is considered an index of prenatal exposure to androgen. Indeed, androgen receptors have been linked to digit length, but estrogen receptors are rarely investigated in this context. Thus, we investigated the association between estrogen receptor 1 (ESR1) genetic polymorphisms and 2D:4D in school-aged children. The 2D:4D ratios were determined using Vernier calipers from photocopies of palms provided by 1800 children aged 7 years who were enrolled in an ongoing prospective cohort study in Hokkaido, Japan. The children were genotyped using cord blood collected at birth for single nucleotide polymorphisms in ESR1, specifically PvuII (T > C, dbSNP: rs2234693), XbaI (A > G, dbSNP: rs9340799), and rs2077647 (A > G). The association between ESR1 polymorphisms and 2D:4D was assessed by multiple linear regression adjusted for potential cofounding factors. Boys with the GG genotype at rs9340799 had a significantly lower 2D:4D in the right hand than boys with the AA/AG genotype (−0.96% lower, 95% confidence interval: −1.68 to −0.24). However, this association was detected only in boys born to non-smoking mothers. No significant differences were found between rs9340799 polymorphisms and 2D:4D among girls. There was also no link between 2D:4D and polymorphisms at rs2234693 and rs2077647. These data suggest that rs9340799 polymorphisms in ESR1 may contribute to digit length and 2D:4D.

Association of Estrogen Receptor 1 Genetic Polymorphisms with Recurrent Spontaneous Abortion Risk.

Background:Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1(ESR1). The polymorphisms of ESR1 were involved in recurrent spontaneous abortion (RSA); however, the association between ESR1 polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESR1 PvuII (-397C/T, rs2234693) and XbaI (-351A/G, rs9340799) polymorphisms and the risk of RSA.Methods:All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3, 2018. Data were processed in the Stata 12.0 software. The odds ratios (OR s) and 95% confidence intervals (95% CIs) were calculated using fixed-effects models (FEM)/random-effects models (REM).Results:Seven case–control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model (OR = 2.40, 95% CI = 1.05–5.50, P = 0.039). Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model (OR = 0.53, 95% CI = 0.33–0.85, P = 0.009) and the dominant genetic model (OR = 0.55, 95% CI = 0.30–0.98, P = 0.042).Conclusions:Generally, there was no significant association between the polymorphisms of ESR1 and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.

Association of estrogen, progesterone and follicle stimulating hormone receptor polymorphisms with in vitro fertilization outcomes

ABSTRACTDespite the advances in in vitro fertilization (IVF), the implantation success rate for infertile women remains approximately only 15%. In this study, we sought to determine whether implantation failure after repeated IVF treatments is influenced by the presence of common variants in estrogen α, progesterone and follicle stimulating hormone receptor genes. The study population included three groups of women: group 1 were 50 women who had the transfer of ≥3 high-quality embryos during the IVF procedure without ever having had a clinical pregnancy; group 2 were 50 women who achieved a clinical pregnancy after ≤3 high-quality embryos transfers and group 3 were 50 control subjects who achieved a clinical pregnancy without any fertility therapy that resulted in a one live-born infant. Genotype analysis was performed using polymerase chain reaction and Sanger sequencing for rs6165, rs6166, rs2234693, rs9340799. While progesterone receptor single nucleotide polymorphism (SNP) was genotyped based on the amplicon size, the repeats for the ESR1 TA-repeat polymorphism were calculated based on the fragment length. A higher frequency of the heterozygote AG genotype was observed in the infertile groups when compared to controls. Significantly, an allele combination of T of rs2234693, A of rs9340799; S of ESR1 (TA), A of rs6166, G of rs6165 and del of PROGINS had a higher frequency in women who had a successful IVF outcome compared to women who had an unsuccessful IVF outcome, indicating a possible protective combined genotype that could reduce a negative outcome during IVF. This study has demonstrated that combining several candidate genes is needed to assess which may play a role in fertility.Abbreviations: CI: confidence interval; COH: controlled ovarian hyperstimulation; DNA: deoxyribonucleic acid; ESR: estrogen receptors; FSH: follicle stimulating hormones; FSHR: FSH receptor; IVF: in vitro fertilization; PGR: progesterone receptors; SNP: single nucleotide polymorphism

Role of FSHR rs6165 and ESR2 rs4986938 polymorphisms in ovarian stimulation of Iranian women who underwent assisted reproduction treatment.

Gonadotropin therapy was used to stimulate the ovary in infertile women who underwent assisted reproduction treatment (ART). Numerous studies indicated that infertile women showed different responses to gonadotropin therapy. Follicle stimulating hormone receptor (FSHR) and Oestrogen receptor (ER) polymorphisms have been reported to involve induction of folliculogenesis and ovarian response to treatment. In the present study, two polymorphisms, namely FSHR rs6165 and ESR2 rs4986938, were investigated in 198 Iranian infertile women aged less than 39 years who underwent ART. After DNA extraction, these polymorphisms were genotyped by TaqMan genotyping assay. According to the number of eggs released during ovulation, the patients were categorized into poor responders (PR) and good responders (GR). The results indicated that the good responders showed lower levels of FSH and LH than poor responders. No association was observed between ESR2 rs4986938 and poor response in Iranian women patients. Instead, FSHR rs6165 showed a strong association with ovarian response to ART (p< 0.05). The obtained results indicated that FSHR rs6165, not ESR2 rs4986938, could be suggested as a candidate marker to predict poor ovarian response.

Association between single nucleotide polymorphisms in estrogen receptor 1/2 genes and symptomatic severity of autism spectrum disorder

BackgroundPrevious studies on etiology of autism spectrum disorders (ASD) have shown strong contribution of hereditary factors. On the basis the heterogeneity in ASD symptoms, it is highly possible that each independent domain of ASD symptom is linked to a different set of genetic risk factors. However, few empirical investigations have been carried out to examine this hypothesis. AimsThe aim of the present study was to investigate the association between single-nucleotide polymorphisms (SNPs) in estrogen receptor genes, which several previous studies have identified as potential risk factors of ASD, and the severity of each independent aspect of ASD symptom within an Asian clinical sample. Method and proceduresWe investigated the association between severities of four ASD symptoms (Social Communication, Social Interaction, Stereotypies and Sensory Abnormalities, and Emotional Regulation) measured by childhood autism rating scale and SNPs in genes of estrogen receptor 1 and 2, ESR1 rs11155819 and ESR2 rs1152582, in 96 Japanese individuals with ASD. Outcomes and resultsThe analysis revealed that severities in the impairment of social interaction and emotional regulation were linked to SNPs in ESR1 rs11155819 and ESR2 rs1152582, respectively. The effect of genotype was not observed for the other aspects of ASD symptoms. Conclusions and implicationsThese findings support our contention that the severity of each ASD symptom domain is determined by a distinct set of genetic risk factors.

Rapid effects of estradiol on aggression depend on genotype in a species with an estrogen receptor polymorphism

The white-throated sparrow (Zonotrichia albicollis) represents a powerful model in behavioral neuroendocrinology because it occurs in two plumage morphs that differ with respect to steroid-dependent social behaviors. Birds of the white-striped (WS) morph engage in more territorial aggression than do birds of the tan-striped (TS) morph, and the TS birds engage in more parenting behavior. This behavioral polymorphism is caused by a chromosomal inversion that has captured many genes, including estrogen receptor alpha (ERα). In this study, we tested the hypothesis that morph differences in aggression might be explained by differential sensitivity to estradiol (E2). We administered E2 non-invasively to non-breeding white-throated sparrows and quantified aggression toward a conspecific 10 min later. E2 administration rapidly increased aggression in WS birds but not TS birds, consistent with our hypothesis that differential sensitivity to E2 may at least partially explain morph differences in aggression. To query the site of E2 action in the brain, we administered E2 and quantified Egr-1 expression in brain regions in which expression of ERα is known to differ between the morphs. E2 treatment decreased Egr-1 immunoreactivity in nucleus taeniae of the amygdala, but this effect did not depend on morph. Overall, our results support a role for differential effects of E2 on aggression in the two morphs, but more research will be needed to determine the neuroanatomical site of action.