Estrogen Receptor Polymorphisms Research Articles

Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in North Indian Population.

In the hypothalamic-pituitary-gonadotrophin (HPG) axis, estrogen plays a key role in the bone maturation regulation and growth plates closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in the North Indian population. Four SNPs of the ESR1 gene (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in 52 ISS patients and 68 controls. Linkage disequilibrium (LD) and haplotyping were done by SNPstat and SHESISplus softwares. Extent of LD was determined by calculating D' and r2 values in SNPs paired combinations. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility as compared to controls. The frequencies of the rs6557177 CC genotype (p=0.030; OR=0.13; 95% CI:0.01-1.10) and rs543650 genotype TT (p =0.043; OR=0.29; 95% CI: 0.09-0.92) were observed to be increased in ISS group as compared with the control group. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 shown strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Our study showed that CC genotype at rs6557177 and TT genotype of rs543650 of ESR1 constitutes risk factor for developing ISS in North Indian children. In the future, these findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

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.

Prediction of medication-related osteonecrosis of the jaws using machine learning methods from estrogen receptor 1 polymorphisms and clinical information.

The purpose of this study was to evaluate the effect of estrogen receptor 1 (ESR1) polymorphisms on the development of medication-related osteonecrosis of the jaws (MRONJ) in women with osteoporosis. A total of 125 patients taking bisphosphonates was evaluated the relationship between MRONJ occurrence and single nucleotide polymorphisms (SNPs) of ESR1. Clinical information was collected, including current age, treatment duration, and comorbidity. Univariate and Multivariable regression analyzes were performed to evaluate the independent predictive factors for MRONJ occurrence. Predictive models were constructed using machine learning methods such as Lasso regression, Random forest (RF), and Support vector machine (SVM). The area under the receiver-operating curve (AUROC) was used to evaluate the performance of a binary classifier. Two SNPs of ESR1 (rs4870056 and rs78177662) were significantly associated with MRONJ development. Patients with variant allele (A) of rs4870056 showed 2.45 times (95% CI, 1.03-5.87) the odds of MRONJ occurrence compared to those with wild-type homozygote (GG) after adjusting covariates. Additionally, carriers with variant allele (T) of rs78177662 had higher odds than those with wild-type homozygote (CC) (adjusted odds ratio (aOR), 2.64, 95% CI, 1.00-6.94). Among demographic variables, age ≥ 72 years (aOR, 3.98, 95% CI, 1.60-9.87) and bisphosphonate exposure ≥48 months (aOR, 3.16, 95% CI, 1.26-7.93) were also significant risk factors for MRONJ occurrence. AUROC values of machine learning methods ranged between 0.756-0.806 in the study. Our study showed that the MRONJ occurrence was associated with ESR1 polymorphisms in osteoporotic women.

Genetic polymorphisms in ESR and FSHβ genes and their association with litter traits in Large White pigs

The estrogen receptor (ESR) gene and follicle-stimulating hormone β (FSHβ) gene are responsible for litter traits. The present study aimed to verify the polymorphisms of ESR and FSHβ and assess their effects on the litter traits in 201 Large White pigs. Four SNPs (g.C669T, g.A1296G, g.C1665T and g.A1755G) were found in ESR. The TT genotype at g.C1665T locus and AA genotype at g.A1755G locus could significantly increase the total litter size of the first litter of American Large White pigs (p < 0.05). Eight SNPs were found in exon 3 of FSHβ. The AA genotype at g.A511G locus, AA and AG genotypes at g.A617G locus, CC and CT genotypes at g.C630T locus, CT and TT genotypes at g.C652T locus, CT and TT genotypes at g.C735T locus, AA and AG genotypes at g.A746G, AA and AG genotypes at g.A921G and CT genotype at g.C678T could significantly increase the litter size of different strains of Large White pigs (p < 0.05). Our study revealed that the genetic variations of ESR and FSHβ were closely related to the litter trait of Large White pigs. Therefore, ESR and FSHβ genes could be used as molecular markers for the genetic selection of Large White pigs.

Genetic Polymorphisms of Estrogen Receptors α and β are Associated with Craniofacial Measurements in Patients With Dentofacial Deformity.

Dentofacial deformities are characterized by abnormalities in craniofacial development that affects the individual's skeletal and occlusion, often causing functional and esthetic problems. In literature, there is an involvement of polymorphisms in estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) genes in craniofacial measurements. The aim of this study was to evaluate a possible association between polymorphisms in ESR1 (rs2234693 and rs9340799) and ESR2 (rs1256049 and rs4986938) genes with cephalometric measurements in individuals with dentofacial deformities. This cross-sectional study was performed with 158 individuals in the preoperative period of orthognathic surgery. The cephalometric measurements obtained through lateral cephalogram using Dolphin Imaging software. For genetic analysis, the DNA extracted from epithelial cells of the oral mucosa and were genotyped using the real-time polymerase chain reaction. The data found submitted to statistical analysis, through the Kolmogorov-Smirnov, Mann-Whitney, and Kruskal-Wallis tests, using the IBM SPSS software version 24.0. Considered a significance level of 0.05. We found association between polymorphisms and cephalometric measurements just in the female sex. The polymorphisms ESR1/rs9340799 ( P= 0.003), ESR1/rs2234693 ( P= 0.026), and ESR2/rs1256049 ( P= 0.046) were associated with the upper gonial angle (Ar-Go-N). The polymorphism ESR2/rs1256049 was also associated with the facial axis-rickets (NBa-PtGn) ( P= 0.004), anterior cranial base (SN) ( P= 0.036), and Y-axis (SGn-SN) ( P= 0.031).

Association of exposure to prenatal perfluoroalkyl substances and estrogen receptor 1 polymorphisms with the second to fourth digit ratio in school-aged children: The Hokkaido study

Per- and Polyfluoroalkyl substances (PFAS) have endocrine-disrupting effects. The ratio of the lengths of the second and fourth digits (2D:4D) is a noninvasive retrospective index of prenatal exposure to sex hormones, and estrogen receptor 1 (ESR1) polymorphisms may contribute to 2D:4D determination. We investigated whether ESR1 polymorphisms modify the effects of prenatal PFAS exposure on 2D:4D. Participants (n = 1024) with complete data in a prospective birth cohort study (the Hokkaido Study) were included, and maternal plasma in the third trimester was used to examine PFAS concentrations. 2D:4D was determined from photocopies of palms of children using Vernier calipers. ESR1 polymorphisms (rs2234693, rs9340799, and rs2077647) were genotyped by TaqMan polymerase chain reaction. PFAS and 2D:4D association with ESR1 polymorphisms was assessed by multiple linear regression adjusted for potential confounding factors. A 10-fold increase in maternal perfluorooctanoic acid (PFOA) concentration was associated with a 1.54% [95% confidence interval (CI): 0.40, 2.68] increase in mean 2D:4D in children with an AA genotype at rs9340799 and a 2.24% (95% CI: 0.57, 3.92) increase in children with an AA genotype at rs2077647. A 10-fold increase in perfluorododecanoic acid (PFDoDA) was associated with a significant increase in 2D:4D in children with the AA genotype [rs9340799, 1.18% (95% CI: 0.02, 2.34); and rs2077647, 1.67% (95% CI: 0.05, 3.28)]. These associations were apparent among males. A significant gene-environment interaction between PFOA or PFDoDA and ESR1 polymorphism was detected. These findings suggest that ESR1 polymorphisms modify the effects of prenatal exposure to PFAS on sex differentiation.

Genetic and serum markers in adult degenerative scoliosis: a literature review.

Literature review. Adult degenerative scoliosis (ADS) is becoming a more prevalent diagnosis with an increasing elderly population. Our objective is to provide a literature review of genetic and serum markers in ADS. A literature review was conducted in the various databases from their inception to July 2020. Studies that reviewed any genetic or serum markers of ADS whether in detection or progression were selected. Studies that reviewed congenital scoliosis or adolescent idiopathic scoliosis (AIS) were excluded. A total of 1447 titles were identified of which 14 were included in the final review. Two papers reported on serum markers pertaining to serum cartilage metabolites and pentosidine. Twelve studies reported on genetic markers including gene polymorphisms in estrogen receptors, parathyroid hormone receptors, interleukin 6, cyclooxygenase-2 (COX-2), COL2A1, GPRIN1, TRAIL, GRIN receptor, RIMS, LBX1 as well as copy number variations. Serum markers of osteoarthritis and sarcopenia have been found to be significantly elevated in ADS patients as well. Numerous polymorphisms have been found in a variety of genes playing key roles in bone formation and regulation. Further research is needed in validating previous studies as well as identifying other biomarkers for patients at risk for developing ADS.

Ex Vivo Evaluation of Red Blood Cell Adhesion and Whole Blood Thrombosis in Pyruvate Kinase Deficiency

IntroductionPyruvate Kinase Deficiency (PKD) is an inherited glycolytic enzymopathy that is characterized by a life-long chronic hemolytic anemia with severe comorbidities. Hypercoagulability due to increased platelet activity caused by nitric oxide sequestration by cell free hemoglobin has been well-described not just in PKD, but in other hemolytic anemias as well, such as e.g., sickle cell disease (SCD). Hypercoagulability is often accompanied by a cascade of pathophysiological events leading to cell oxidative damage, endothelial activation, and changes in both cell stability and adhesive properties. Increased red blood cell (RBC) adhesion and hypercoagulability may impair microvascular blood flow. Despite these well-recognized rheological changes that are similar to those that occur in other hemolytic anemias, the relationship between baseline erythrocyte adhesion and thrombosis potential have not been well-studied in PKD.Methods10 PKD subjects and 5 healthy controls were recruited under the IRB-approved protocol from Wayne State University. Flow adhesion of whole blood to vascular cell adhesion molecule-1 (FA-WB-VCAM) was performed by flowing whole blood (1:1 dilution) through a microfluidic channel for 3 minutes (1 dyne/cm 2 shear stress, 1.67Hz pulse frequency). Flow adhesion avidity of the whole blood sample to VCAM-1 (FAAv-WB-VCAM), representing the strength of the RBC-VCAM-1 adhesive interactions, was assessed by quantifying adhesion following sequential increase in shear (5, 10, 20 dyne/cm 2). Thrombin generation assay was conducted using platelet poor plasma with and without thrombomodulin and microparticles (MP) as previously published [1]. Clotting time - reported as lag time (LT), time to peak (ttPeak) and peak height (velocity and amount of net thrombin production), and endogenous thrombin potential (ETP), representing number of substrates potentially convertible by thrombin, were measured. Significance was at p < 0.05.ResultsFA-WB-VCAM at baseline sample hematocrit was significantly elevated (Figure 1) in PKD subjects (808±377 cells/mm², n=10) compared to healthy controls (6±4 cells/mm², n=4) and even to our previously reported steady state levels in sickle cell samples (290±50 cells/mm² [2]. Thrombin generation profiles were similar between PKD subjects and healthy controls with the exception of the thrombin generation index (PPP+TP/PPP)*100ETP that was significantly (p<<0.01) elevated in citrated plasma of PKD subjects (92.9±6.8) as compared to healthy controls (68.6±11.9). For PKD subjects, FA-WB-VCAM correlated significantly with platelet counts (R²=0.81, p<0.05), and FAAv-WB-VCAM was negatively correlated with platelet (P=0.03, R 2=0.5), but not with erythrocyte-derived microparticles (MP). Platelet-derived MP strongly correlated with thrombin generation (ETP, p<0.01, R 2=0.76) but not with LT or ttPeak of thrombin generation. Red blood cell MP were significantly (p=0.02) decreased in splenectomized patients (200±170, n=7) vs. non-splenectomized subjects (2090±1860, n=3). LT and ttPeak were significantly longer in PKD subjects with thrombosis history than without.ConclusionsPKD subjects in this study had elevated RBC adhesive properties similar to that observed in SCD, confirming that pathologic RBC membrane damage resulting in increased adhesion is a common feature of hemolytic anemias. The hemoglobin level of 7.8±1.1 g/dL (mean±SD) for PKD patients was within 6 to 11 g/dl range of hemoglobin levels typical for SCD. There was no significant difference in any other measured parameters (thrombin generation, adhesion avidity, microparticles data). Thrombin generation in PKD subjects was not consistent with hypercoagulability. Based on these observations, pathologic RBC adhesion may be both a novel a mechanism driving hypercoagulability in individuals with PKD. Further studies to determine whether RBC-modifying therapies may decrease thrombosis risk in PKD are warranted.1. Zia A, Callaghan MU, Callaghan JH, et al. Hypercoagulability in adolescent girls on oral contraceptives - global coagulation profile and estrogen receptor polymorphisms. Am J Hematol, 2015;90:725-312. Pittman DD, Hines PC, Beidler D, et al. Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) by patient-reported outcomes, actigraphy, and biomarkers. Blood. 2021;137(15):2010-20 [Display omitted] DisclosuresHines: Functional Fluidics: Current holder of stock options in a privately-held company. Gao: Functional Fluidics: Current Employment. Herppich: Functional Fluidics: Ended employment in the past 24 months. Kwiatkowski: Imara: Consultancy, Research Funding; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Sangamo: Research Funding; Bioverativ: Research Funding; Vertex: Research Funding; Silence Therapeutics: Consultancy; bluebird bio: Consultancy, Research Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Chiesi: Research Funding; CRISPR: Research Funding. Tarasev: Functional Fluidics: Current holder of stock options in a privately-held company.

Lack of association between delayed tooth emergence and single nucleotide polymorphisms in estrogen receptors

The purpose of the study was to investigate the association between single nucleotide polymorphisms (SNPs) in genes encoding estrogen receptors (ESR1 and ESR2, respectively) and delayed tooth emergence (DTE). This cross-sectional study was composed of biological unrelated children of both sexes, age ranging from 11 to 13 years old. DTE was defined when the successor primary tooth was still present in the oral cavity after its exfoliation time or the absence of the permanent tooth emergence into the oral cavity. Children were diagnosed with DTE when they had at least one delayed permanent tooth, according to age of exfoliation of each tooth proposed by The American Dental Association. Genomic DNA from saliva was used to evaluate the SNPs in ESR1 (rs9340799 and rs2234693) and ESR2 (rs1256049 and rs4986938) using Real-Time PCR. Chi-square or Fisher exact tests and Logistic Regression adjusted by age and gender were performed. SNP-SNP interaction was accessed by multifactor dimensionality reduction (MDR) analysis also adjusted by gender and age. The established alpha of this study was 5%. Among 537 included children, 296 (55%) were in the "DTE" group and the 241 (45%) were in the "Control" group. Age and gender were not statistically different among the groups (p>0.05). Genotype distribution of the SNPs rs9340799, rs2234693, rs1256049 and rs4986938 were not associated with DTE (p> 0.05). The models elected by MDR were not statistically significant either. Conclusions: The studied SNPs in ESR1 and ESR2 were not associated with permanent DTE.

Allelic variability of estrogen receptor (ESR) gene and its effect on litter traits of Doom pigs.

The present study was conducted to identify the polymorphism of estrogen receptor (ESR) gene and its biological association with litter traits (litter size at birth, litter size at weaning, litter weight at birth and litter weight at weaning) of Doom pigs native to Assam. A total of 50 adult pigs (12 males and 38 females) chosen randomly from three different herds (Herd I, Herd II, and Herd III) were utilized in the present study. Detection of polymorphism of ESR gene was done by means of PCR-RFLP method. The amplified PCR product was digested with Pvu II restriction enzyme. PCR-RFLP analysis of ESR gene revealed polymorphic banding pattern. Two genotypes viz. AA and AB were identified. AA genotype yielded one fragment (120 bp) and AB genotype yielded three fragments (120, 65, and 55 bp). BB genotype was not found in the population under study. The frequencies of A and B alleles were found to be 0.650 and 0.350, respectively, and the genotypic frequencies of ESR gene were found to be 0.300 and 0.700 for AA and AB genotypes, respectively. There was no significant (P > 0.05) effect of ESR genotype on litter traits and the population under study was not in Hardy-Weinberg Equilibrium for ESR gene. Clustal W Multiple alignment of partial sequence of ESR gene revealed single nucleotide changes at 33, 65, 70, 83, and 92nd nucleotide positions. The presence of Pvu II polymorphism and identification of single nucleotide variation of ESR gene opens interesting prospects for improvement oflitter traits in Doom pig through selective breeding program, especially based on marker-assisted selection.

Polymorphism of PvuII, Xba1, and SNP 12 Estrogen Receptor 1 (ESR1) in Hipospadias Patients at Tertiary Hospital Center.

IntroductionThe prevalence of hypospadias ranges between 1: 250 to 300 per live birth. Estrogen exposure has been associated with the increasing incidence of hypospadias in humans and a significant relationship between Estrogen Receptor 1 (ESR1) polymorphisms and hypospadias was determined from the previous study. This study aims to determine the proportion of ESR1 polymorphism.MethodsThis was a descriptive study aimed to find the incidence of ESR1 gene polymorphism in hypospadias patients visiting the Urology Outpatient Unit of the Hasan Sadikin Bandung Hospital who will undergo hypospadias surgery. Deoxyribonucleic acid (DNA) was performed using foreskin of hypospadias patient during the surgery then being extracted and will be analyzed using polymerase chain reaction (PCR) sequencing.ResultsThirty eight samples of hypospadias were identified, 5 samples were unable to sequence and 33 samples were successfully sequenced using the PCR method. The Pvull ESR1 gene was dominated by the T allele which is a wild-type allele and the genotype containing the T allele, namely TT + TC (57,2%). Normal genotype (TT) were more frequent in distal hypospadias, and Heterozygous polymorphisms (TC) was higher in proximal hypospadias. The ESR1 Xba1 gene polymorphism was dominated by the A allele which is a wild-type allele and the AA + AG genotype (76,1%). Normal genotype (AA) was more frequent in distal hypospadias, and both heterozygous hypospadias (AG) and homozygous hypospadias (GG) were found only in proximal hypospadias. The ESR1 SNP 12 gene polymorphisms were found in the combination of genotypes that played a role, namely GA + AA (81%) and the G allele which is a wild-type allele. Heterozygous polymorphisms (GA) was the most finding genotype and more frequent in proximal hypospadias.ConclusionESR1 gene polymorphisms (PvuII, XbaI, and SNP 12) were found in hypospadias patients. ESR1 polymorphisms may correlate with the severity of hypospadias. Further research with a larger sample and better hypospadias grouping is needed to confirm.

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

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. 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. 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). 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.

Association analysis of ESR gene polymorphism and carcass traits in egg quails (Coturnix coturnix)

The polymorphism of estrogen receptor (ESR) gene was detected by PCR-RFLP in China yellow, Korean and Beijing white quails and the association between ESR gene polymorphism and carcass traits of egg quails was analyzed. The results showed that there were three genotypes including CC, CT and TT detected in exon 1 and exon 8 of ESR gene in egg quails. The frequencies of CC genotype in exon 1 of ESR gene were the highest in China yellow, Beijing white and Korean quail (0.515, 0.614, 0.723). The highest frequencies of TT genotype in exon 8 of ESR gene were detected in Beijing white and Korean quails (0.618 and 0.540), while the highest frequency of CT genotype was detected in China yellow quail (0.476). As demonstrated in this study, there were significant correlations between exon 1 of ESR gene and body weight, carcass weight, breast muscle weight, heart weight and percentage of leg muscles in egg quails (P&lt;0.05).

Effect of ESR, FSHB and PRLR Genes on Sperm Traits of Landrace and Yorkshire Boars in the Tropical Environmental Conditions of Vietnam

Background: Fertility traits in pigs made a restricted progress through traditional selection. Applying marker assisted selection could improve these traits. The aim of the study was to investigate the effects of candidate genes Estrogen Receptor (ESR), Follicle Stimulating Hormone Beta (FSHB) and Prolactin Receptor (PRLR) on sperm quality traits of Landrace and Yorkshire boars under tropical conditions in Northern Vietnam.Methods: A total of 6306 ejaculates from 140 boars (92 Landrace and 48 Yorkshire) were collected to estimate sperm ejaculate volume (VOL), spermatozoon motility (MO), sperm concentration (CO) and total number of spermatozoon in ejaculate (NT). Ear tissue samples were collected for genotype identification of SNP present in ESR, FSHB and PRLR genes using PCR-RFLP technique. A mixed model was used to test the effect of different genetic and non-genetic factors on the sperm quality traits.Result: The genotype frequencies of ESR, FSHB and PRLR were in Hardy-Weinberg equilibrium for each breed. Age of boars and month of the year had significant effect on all the sperm quality traits (P less than 0.01) while effect of breed was found to be non-significant on all the sperm quality trait. FSHB gene significantly (P less than 0.05) affected VOL, MO and CO. Boars with BB genotype showed positive effect on VOL but negative effect on MO and CO in comparison with AA genotype boars. ESR gene showed only effect on VOL while PRLR affected only MO. Boars with AA and AB genotypes of ESR gene had a significantly higher VOL than those with BB genotype (P less than 0.05). For PRLR gen, AB genotype was associated with higher MO than AA genotype (P less than 0.05). These results suggest a possibility of using the existing polymorphisms in ESR, FSHB and PRLR genes to improve some sperm traits of Landrace and Yorkshire boars.

Impact of ESR1 Polymorphisms on Risk of Breast Cancer in the Chinese Han Population

BackgroundThe estrogen receptor-1 (ESR1) gene encodes estrogen receptor-α, which is a major biomarker in the development of breast cancer. This study aimed to investigate the effect of ESR1 polymorphisms on breast cancer in Chinese Han women. Materials and MethodsWe genotyped 4 candidate single nucleotide polymorphisms (SNPs) in ESR1 among 503 patients with breast cancer and 503 healthy people using the Agena MassARRAY platform. The association between ESR1 polymorphisms and breast cancer risk was evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) under 4 genetic models. The HaploReg v4.1 and GEPIA database were used for SNP functional annotation and ESR1 expression analysis, respectively. ResultsThe T allele of rs9383938 in ESR1 was significantly associated with an increased breast cancer risk (OR, 1.26; 95% CI, 1.05-1.50; P = .013). In genetic models, rs9383938 increased breast cancer risk in the codominant model (OR, 1.54; 95% CI, 1.07-2.22; P = .021), the dominant model (OR, 1.31; 95% CI, 1.01-1.68; P = .040), and the additive model (OR, 1.24; 95% CI, 1.04-1.48; P = .017). Stratification analysis showed that rs9383938 and rs2228480 raised the breast cancer susceptibility in individuals aged younger than 52 years old. Rs1801132 of ESR1 was significantly associated with the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 in the allele model and genetic models (P < .05). ConclusionsThis study demonstrated that ESR1 polymorphisms might influence breast cancer susceptibility in the Chinese Han population. Further mechanism studies are needed to confirm the contribution of ESR1.

Association of estrogen receptor 1 (ESR1) gene (rs2234693) polymorphism, ESR1 promoter methylation status, and serum heavy metals concentration, with breast cancer: A study on Iranian women population

Backgroundgenetic and epigenetic alteration of estrogen receptor genes could be associated with the development of breast cancer. In addition, demographic and environmental factors may play a role in this issue. This work was performed to investigate the effect of Estrogen Receptor 1 (ESR1) puv II (rs2234693 T > C) polymorphism, the methylation status of ESR1 promoter as well as the serum level of different heavy metals, including lead, cadmium, zinc, copper, and chromium on susceptibility to breast cancer. Material and methods60 breast cancer patients and 60 healthy controls from the province of Mazandaran, Iran, participated in this case-control study. Restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and Quantitative methylation-specific PCR were conducted to determine ESR1 PvuII (rs2234693 T > C) polymorphism and methylation status of ESR1 promoter, respectively. Also, flame atomic absorption was used to determine the serum level of heavy metals. ResultThe association of TC and CC + TC genotypes with a higher risk of breast cancer was found. In addition, no difference for the methylation status of ESR1 promoter among case and control individuals was observed. In addition, there was an association between serum level of chromium with breast cancer, while the serum level of other heavy metals was not significantly different between the two groups. Conclusionour study suggests ESR1 polymorphism and environmental pollutants as two main contributing factors in breast cancer susceptibility in Iranian women. However, further investigations are needed on this issue.

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.