ESR1 Polymorphisms Research Articles

Ассоциация полиморфизма генов COL1A1, ESR1 и VDR с риском развития дисфункции тазового дна у женщин после родоразрешения

Ассоциация полиморфизма генов COL1A1, ESR1 и VDR с риском развития дисфункции тазового дна у женщин после родоразрешения

Follicle-Stimulating Hormone Receptor and Estrogen Receptor Gene Polymorphisms in Women With Discordant Follicle-Stimulating Hormone and Anti-Mullerian Hormone Levels.

Objective This study aimed to investigate follicle-stimulating hormone receptor (FSHR) polymorphisms(Thr307Ala and Asn680Ser), estrogen receptor 1 (ESR1) polymorphisms (PvuII and XbaI), and ESR2 polymorphisms (RsaI and AluI) in Turkish women with follicle-stimulating hormone (FSH) and anti-Mullerian hormone (AMH) discordance. Method Genotyping was performed in 60 patients aged 21-35 with FSH-AMH discordance and/or low ovarian reserve and 20 age-matched controls with normal FSH and AMH levels. The patients were investigated in four groups of 20 women according to their FSH and AMH levels. Groups 1, 2, 3, and 4 were as follows: normal FSH and low AMH levels, normal AMH and high FSH levels, high FSH and low AMH levels, and normal FSH and AMH levels. Genomic DNA was obtained from 3 cc peripheral blood, and polymorphisms were analyzed using TaqMan genotyping assays. Relations between groups of categorical variables were analyzed with a chi-square test. Differences between the groups were assessed using a student's t-testor Mann-Whitney U test. Results Women with discordant FSH and AMH levels (group 1 and group 2) were not statistically different from women with concordant FSH and AMH levels (group 3 and group 4) in terms of FSHR, ESR1, and ER2 single nucleotide polymorphisms (SNPs). Body mass index (BMI) was statistically significant between groups 1 and 2 as well as groups 2 and 3 (p = 0.004). Conclusions This study showed that FSHR, ESR1, and ESR2 SNPs have not had any effect on AMH-FSH discordance in reproductive age Turkish women.

Polymorphisms in ESR1 and CYP19A1 genes in postmenopausal women with knee osteoarthritis

To date, a number of studies have been carried out to investigate the role of polymorphisms in estrogen receptor (ESR) and aromatase (CYP19A1) genes in knee osteoarthritis. However, the obtained results are contradictory and are not sufficient to formulate final conclusions. Purpose of the study: to investigate the associations of the rs2234693 and rs9340799 polymorphisms in ESR1 gene and the rs2414096 and rs936306 polymorphisms in CYP19A1 gene with knee osteoarthritis in postmenopausal women. Material and methods. Molecular genetic studies were performed in 157 postmenopausal women with knee osteoarthritis. The control group consisted of 326 women of the same age without signs of joint disease. Results. A comparative analysis of the results showed an association of the AA genotype of the rs2414096 polymorphism in CYP19A1 gene with increased susceptibility to knee osteoarthritis (p = 0,022). For the second polymorphism in CYP19A1 gene (rs936306), as well as for two polymorphisms in ESR1 gene (rs2234693 and rs9340799), no association with osteoarthritis was established (p > 0,05). Conclusion. The obtained results indicate the need for further larger-scale studies of genes role involved in estrogen metabolism in the development of knee osteoarthritis in postmenopausal women.

Association of the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) Polymorphisms With Risk of Coronary Artery Disease in Iranian Patients.

Coronary artery disease (CAD) is a devastating illness and a leading cause of death worldwide, primarily caused by atherosclerosis resulting from a genetic-environmental interaction. This study aimed to investigate the relationship between the ESR1 (rs9340799), OLR1 (rs3736234), LIPC (rs2070895), VDR (rs2228570), and CETP (rs708272) polymorphisms, lipid profile parameters, and CAD risk in a southeast Iranian population. A total of 400 subjects (200 CAD patients with hyperlipidemia and 200 healthy controls) were enrolled in this case-control study. Five selected polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. For all single nucleotide polymorphisms (SNPs), the population under study was in the Hardy-Weinberg equilibrium. The T-risk allele frequency of rs2228570 was associated with an increased risk of CAD. The TT and CT genotypes of rs2228570 had also been associated with the risk of CAD. Additionally, the TT genotype was associated with higher serum low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) levels. The GG genotype of the rs3736234 was associated with higher body mass index (BMI) and triglyceride (TG) levels, and the AA genotype of the rs708272 was associated with higher HDL-c levels. Based on these findings, we propose that the VDR (rs2228570) polymorphism was associated with serum HDL-c and LDL-c levels and may serve as potential risk factors for CAD within the Iranian population. Moreover, rs3736234 and rs708272 influence the concentrations of TG and HDL-c, respectively. These findings provided insights into the complex interplay between genetic variations, cardiovascular risk, and lipid metabolism.

Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study

BackgroundPolycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, and reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, and hirsutism. Mutations in the estrogen receptor genes ESR1 and ESR2, involved in normal follicular development and ovulation, can contribute to development of the PCOS. The present study focuses on investigating the potential correlation between single nucleotide polymorphisms (SNPs) of ESR1 and ESR2 genes and the incidence of this syndrome.MethodsFor this study, SNPs in ESR1 and ESR2 genes were retrieved from the ENSEMBL database and analyzed for their effect on mutated proteins using different bioinformatics tools including SIFT, PolyPhen, CADD, REVEL, MetaLR, I-Mutant, CELLO2GO, ProtParam, SOPMA, SWISS-MODEL and HDDOCK.ResultsAll the SNPs documented in the present study were deleterious. All the SNPs except rs1583384537, rs1450198518, and rs78255744 decreased protein stability. Two variants rs1463893698 and rs766843910 in the ESR2 gene altered the localization of mutated proteins i.e. in addition to the nucleus, proteins were also found in mitochondria and extracellular, respectively. SNPs rs104893956 in ESR1 and rs140630557, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene significantly changed the secondary structure of proteins (2D). SNPs that markedly changed 3D configuration included rs1554259481, rs188957694 and rs755667747 in ESR1 gene and rs1463893698, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene. Variants rs1467954450 (ESR1) and rs140630557 (ESR2) were identified to reduce the binding tendency of ESRα and β receptors with estradiol as reflected by the docking scores i.e. -164.97 and -173.23, respectively.ConclusionDue to the significant impact on the encoded proteins, these variants might be proposed as biomarkers to predict the likelihood of developing PCOS in the future and for diagnostic purposes.

The Influence of ESR2 Gene Polymorphisms on Susceptibility to Hepatitis B Virus-Related Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) represents an estrogen-dependent tumor. The action of estrogen is regulated via estrogen receptor (ER). Polymorphisms in ERα gene, ESR1, are known to be related to HCC susceptibility among people carrying chronic hepatitis B (CHB). But the effect of ERβ on HCC is still largely unclear, and studies about the genetic variability of ESR2 and HCC are rare. For understanding ESR2's effect on HCC, this work tested two polymorphisms in the ESR2 gene promoter as well as the associations with CHB, HCC, and hepatitis B virus (HBV)-related liver cirrhosis (LC) among the Guangxi population. This work enrolled a total of 137 CHB, 136 LC, and 149 HBV-related HCC patients, together with 146 normal subjects. ESR2 polymorphisms rs3020449 and rs2978381 were examined using the SNaPshot genotyping technique. The AG genotype and dominant model of rs3020449 were related to the decreased CHB susceptibility. In both the overall and subgroup analyses, no associations were observed with the remaining models in all patient groups (those with CHB, HBV-related LC, and HCC), but associations were found between the dominant (TC+CC vs TT) and allele models (C vs T) of rs2978381 and increased HBV-related LC and HCC susceptibility, but not CHB. These findings suggest that rs3020449 polymorphism of ESR2 gene makes great contribution to the decreased CHB risk and that rs2978381 significantly contributed to higher risks of HBV-related LC and HCC.

Assessing the association of ESR1 polymorphisms with male infertility in Vietnamese population

Male infertility is a prevalent global concern, impacting an estimated 7% of the male population. Many single nucleotide polymorphisms (SNPs) linked to idiopathic male infertility have been discovered since the 1990s, including two intronic SNPs of the estrogen receptor α gene (ESR1), namely rs9340799 and rs2234693. However, the associations of the two SNPs with male infertility have yielded inconsistent results across different populations. In this study, we aimed to assess the association of ESR1 rs9340799 and ESR1 rs2234693 with male infertility in a cohort of Vietnamese individuals consisting of 154 fertile men and 146 infertile men. Genotyping ESR1 rs9340799 and ESR1 rs2234693 for 300 samples was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR - RFLP). The frequencies of genotypes and alleles were analyzed using bioinformatic tools. The genotype distributions of ESR1 rs9340799 and ESR1 rs2234693 followed Hardy-Weinberg equilibrium, but no association of the two SNPs with male infertility was established (p > 0.05) in the additive, dominant, recessive, and allele models. Notably, the haplotype analysis revealed a strong association between the haplotype GT and a decreased risk of male infertility (OR = 0.226; 95% CI = 0.106 - 0.484; p < 0.001). The findings provide additional knowledge about the roles of single nucleotide polymorphisms in male infertility in the Vietnamese population.

Correlation between ESR1 and APOE gene polymorphisms and risk of osteonecrosis of the femoral head: a case–control study

BackgroundOsteonecrosis of the femoral head (ONFH) is a disease with a high disability rate, and genetic factors are closely related to its pathogenesis. This study aimed to investigate the possible correlation between ESR1 and APOE gene polymorphisms and the risk of ONFH.MethodsIn this case–control study, the potential association between three genetic variants (rs2982573 C < T, rs10872678 C < T, and rs9322332 A < C) of the ESR1 gene and two genetic variants (rs7259620 A < G and rs769446 C < T) of the APOE gene with the risk of ONFH was investigated. Correlations between gene polymorphisms and ONFH risk were assessed using logistic regression analysis, with calculation of odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe overall analysis demonstrated that rs9322332 in the ESR1 gene exhibited a correlation with a decreased risk of ONFH under the homozygous (AA vs.CC: OR = 0.69, 95% CI [0.53–0.90], p = 0.006), dominant (CA + AA vs. CC: OR = 0.70, 95% CI [0.54–0.90], p = 0.006), and additive (OR = 0.79, 95% CI [0.66–0.95], p = 0.013) models. The stratification analysis revealed that rs9322332 was linked to a lower risk of ONFH in subgroups characterized by individuals aged over 51 years and non-smokers. Nevertheless, there were no notable correlations found between ESR1 rs2982573 and rs10872678, as well as APOE rs7259620 and rs769446, with the risk of ONFH.ConclusionESR1-rs9322332 is closely linked to a decreased risk of ONFH, thereby enhancing our understanding of the relationship between gene polymorphisms and ONFH.

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.

Molecular genetic determinants of stress urinary incontinence in women: Prospective comparative study

Aim. To identify the molecular genetic determinants of stress urinary incontinence (UI) in women.&#x0D; Materials and methods. A comparative study involving 120 women was conducted. Group 1 (main group) included 80 women with UI. Group 2 (comparison group) included 40 women without UI. Statistic data processing was performed using the Excel software package, SPP Statistics 22.0, Statistica for Windows 10 (TIBCO Software Inc., Palo Alto, CA, USA). The mean and standard deviation were reported for quantitative variables with a normal distribution. The statistical hypotheses on the absence of intergroup differences for quantitative variables with normal distribution were verified using Student's test. The absolute and relative values (in percent) were reported for qualitative variables. The chi-square test was used to verify the statistical hypotheses.&#x0D; Results. Molecular genetic predictors of UI in women are the carriage of polymorphisms of the estrogen receptor gene ESR1:-351_G and the type I collagen gene COL1A1:1546_T. These polymorphisms can be considered as genotypes of "risk" since their carriage is associated with an increased risk of UI.&#x0D; Conclusion. Genetically determined disorders of the estrogen receptor function and type I collagen synthesis can be one of the essential mechanisms of stress incontinence occurrence. Studying molecular genetic determinants of stress incontinence can provide a deeper understanding of its pathogenetic mechanisms and develop a personalized approach to surgical correction.

Antiidiotypic antibodies to estradiol and gene polymorphisms of α and β estrogenic receptors in breast cancer patients

Markers for identification of ER+/PR breast cancer (BC) risks and conversion of ER+/ER+ to ER-/PR- tumors are necessary for effective prevention and therapy of BC by the selective ER – modificators. Purpose – To reveal the proposed associations of gene polymorphisms of ESR1 and ESR2 and antiidiotypic antibodies to estradiol (IgG2-E2) with ER+/PR+ BC risk and conversion of ER+/PR+ to ER-/PR- tumors and to study the interrelations between gene variants of ESR and IgG2-E2 in healthy women and BC patients. Polymorphic loci of ESR1 (rs2234693) and ESR2 (rs4986938) were studied by the real time PCR in 370 healthy women and 1169 BC patients. Tumor tissues ER and PR were detected by the standard immunohistochemical methods. Serum IgG2-E2 were studied using non-competitive enzyme immuno-assay. TT, TC and CC genotypes of ESR1 were revealed with the equal frequency in healthy women and BC patients I stage. Homozygotes GG of ESR2 were detected rarely, but AA frequently in BC patients with ER+/PR+ tumors at the I stage, than in healthy women женщин (44.0% and 14.2% vs 52.7 and 8.4%, respectively; p=0.005). The low levels of IgG2-ES were revealed more rarely but high levels more frequently in BC patients with ER+/PR+ tumors at the I stage, that in healthy donors (39.8% and 60.2% vs 58.0% and 42.0%, respectively; p=0.0002). Decreasing of ER+/PR+ tumors proportion and corresponding increasing of ER-/PR- tumors from I stage to II–IV stages (71.7% to 58.9% and 13.9% to 23.1%; p=0.006) were revealed in TC heterozygotes of ESR1 only. The same conversion of ER+/PR+ tumors to ER-/PR- were detected in GG homozygotes of ESR2 (p=0.004). There have been the similar ER/PR transformation in BC patients with high IgG2-E2 levels (74.7% to 57.6% and 11.3%, to 25.0%, respectively, p&lt;0.0001). High and low IgG2-E2 levels were detected with the same proportions at the any genotypes of ESR1 and ESR2 in healthy women or in BC patients. ESR1-2 gene polymorphisms and serum IgG2-E2 levels may be used as independent markers for prediction of ER+/PR+ and for ER+/PR+ to ER-/PR- tumors conversion during BC progression.

Polymorphism of Estrogen Receptor Genes and Its Interactions With Neurodevelopmental Genes in Attention Deficit Hyperactivity Disorder Among Chinese Han Descent.

Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder with significant gender differences. The sexual dimorphism of ADHD may be associated with estrogen acting through estrogen receptors (ESR). This study investigates the impact of ESR gene polymorphism and its interactions with neurodevelopmental genes on ADHD susceptibility. The study compared genotyping data of single nucleotide polymorphisms in ESR1 and ESR2 in 1,035 ADHD cases and 962 controls. The gene-gene interactions between ESR genes and three neurodevelopmental genes (brain-derived neurotrophic factor [BDNF], synaptosomal-associated protein of 25 kDa gene [SNAP25], and cadherin-13 [CDH13]) in ADHD were investigated using generalized multifactor dimensionality reduction and verified by logistic regression analysis. The G allele of rs960070/ESR2 (empirical p=0.0076) and the A allele of rs8017441/ESR2 (empirical p=0.0426) were found significantly higher in ADHD cases than in the controls but not in male or female subgroups. Though no difference was found in all subjects or females, the A allele of rs9340817/ESR1 (empirical p=0.0344) was found significantly higher in ADHD cases than controls in males. We also found genetic interaction models between ESR2 gene, neurodevelopmental genes and ADHD susceptibility in males (ESR2 rs960070/BDNF rs6265/BDNF rs2049046/SNAP25 rs362987/CDH13 rs6565113) and females (ESR2 rs960070/BDNF rs6265/BDNF rs2049046) separately, though it was negative in overall subjects. The ESR gene polymorphism associates with ADHD among Chinese Han children, with interactions between ESR genes and neurodevelopmental genes potentially influencing the susceptibility of ADHD.

Overall survival of breast cancer patients in association with ESR1 polymorphism

Breast cancer (BC) is the most common carcinoma in women. Genetic polymorphism in estrogen receptor-α (ESR1) gene is involved in alteration in receptor expression, function and evolving as important determinant of breast cancer susceptibility. The present study aimed to evaluate single nucleotide polymorphism (SNP) in breast carcinoma to find out co-relation with overall survival (OS) of breast carcinoma patients. In present study, overall survival of two hundred breast cancer patients with single nucleotide polymorphism was studied in detail. OS was evaluated by Kaplan-Meier method and then analysed with the log-rank test. The cox regression method was used for analyzing data of survival, hazard ratio estimation and its confidence interval value. The significant association of OS was observed with AG genotype of rs9340799 and rs373404617 (Log-rank χ2 = 18.1658, DF = 2, p = 0.0351; χ2 = 5.7632, DF = 2, p = 0.0560 respectively). The genotypes of ESR1 SNP rs9340799 and rs373404617 were predictive of good outcomes of breast cancer. This study suggests that overall survival studies are helpful in investigating progression or regression of the disease which is required for perfect management of breast carcinoma. Future directions include genetic and proteomic-based approaches for breast carcinoma development and progress.

ESR2 polymorphisms on prostate cancer risk: A systematic review and meta-analysis.

This meta-analysis was performed to address the association of 2 ESR2 gene polymorphisms (rs1256049 and rs4986938) with susceptibility to cancer. An extensive literature search for eligible candidate gene studies published before May 10, 2022, was conducted in PubMed, Medline, and Web of Science. The search strategy was as follows: (ESR2 OR ERβ OR ER beta OR estrogen receptor beta) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (PCa OR PC OR prostate cancer). Potential sources of heterogeneity were sought out via trial sequential analysis, subgroup, and sensitivity analysis. Overall, a total of 10 articles involving 18,064 cases and 19,556 controls for 2 polymorphisms of the ESR2 gene were enrolled. In the stratified analysis of rs1256049, we found that Caucasians might be correlated with an increased risk of prostate cancer (PCa), while less susceptibility was found in Asians. We observed that rs4986938 was not associated with PCa risk. ESR2 rs1256049 polymorphism is associated with a higher risk of PCa in the Caucasian population and a lower risk of PCa in the Asian population.

Association of Polymorphisms in FSHR, INHA, ESR1, and BMP15 with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) refers to two or more unsuccessful in vitro fertilization embryo transfers in the same individual. Embryonic characteristics, immunological factors, and coagulation factors are known to be the causes of RIF. Genetic factors have also been reported to be involved in the occurrence of RIF, and some single nucleotide polymorphisms (SNPs) may contribute to RIF. We examined SNPs in FSHR, INHA, ESR1, and BMP15, which have been associated with primary ovarian failure. A cohort of 133 RIF patients and 317 healthy controls consisting of all Korean women was included. Genotyping was performed by Taq-Man genotyping assays to determine the frequency of the following polymorphisms: FSHR rs6165, INHA rs11893842 and rs35118453, ESR1 rs9340799 and rs2234693, and BMP15 rs17003221 and rs3810682. The differences in these SNPs were compared between the patient and control groups. Our results demonstrate a decreased prevalence of RIF in subjects with the FSHR rs6165 A>G polymorphism [AA vs. AG adjusted odds ratio (AOR) = 0.432; confidence interval (CI) = 0.206-0.908; p = 0.027, AA+AG vs. GG AOR = 0.434; CI = 0.213-0.885; p = 0.022]. Based on a genotype combination analysis, the GG/AA (FSHR rs6165/ESR1 rs9340799: OR = 0.250; CI = 0.072-0.874; p = 0.030) and GG-CC (FSHR rs6165/BMP15 rs3810682: OR = 0.466; CI = 0.220-0.987; p = 0.046) alleles were also associated with a decreased RIF risk. Additionally, the FSHR rs6165GG and BMP15 rs17003221TT+TC genotype combination was associated with a decreased RIF risk (OR = 0.430; CI = 0.210-0.877; p = 0.020) and increased FSH levels, as assessed by an analysis of variance. The FSHR rs6165 polymorphism and genotype combinations are significantly associated with RIF development in Korean women.

Genetic variants of IL-10, TGFβ, FGF1, ESR1, MMP1 and WNT4 genes and their association with endometriosis in Iranian women

BackgroundThe complex interaction of genetics, environmental, hormonal, and immunologic factors are involved in the pathogenesis of endometriosis (EMT). This study aimed to investigate the association of controversial and candidate single nucleotide polymorphisms (SNPs) in IL-10 (rs1800872), TGFβ (rs1800469), FGF1 (rs34011), ESR1 (rs9340799; rs2234693), MMP1 (rs1799750), and WNT4 (rs16826658) with EMT in Iranian women with endometriosis. Materials and methodThe seven SNPs in the candidate genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 101 individuals with EMT and 142 healthy ones as a control group. ResultsOur study revealed a significant association of the FGF1–1385 A/G genotype with the developing EMT in our population (p value = 0.041). However, no significant result was found for other candidate genotypes and alleles in susceptibility to EMT. ConclusionFGF1–1385 A/G SNP genotypes might be correlated with the pathogenesis of EMT in Iranian women.

Polymorphisms in hormonal-related genes might be associated with variations in permanent tooth crown size.

The variability in tooth crown size (TCS) is influenced by genetic factors and might be regulated by the difference in hormonal response. This study aimed to evaluate the association between variations in TCS of permanent teeth with associated factors and genetic polymorphisms in hormonal-related genes (ESR1, ESR2 and PTH). This cross-sectional study involved dental casts from 86 individuals of both sexes. Dental casts were used to determine the maximum TCS of all fully erupted permanent teeth (except third molars) in the mesiodistal (MD) and buccolingual (BL) dimensions. Data such as sex, ethnicity, dental group (incisor, canine, premolar and molar), dental arch (upper and lower) and genetic polymorphisms of hormonal-related genes were used. The DNA from each patient was collected to evaluate the genetic polymorphisms in ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938) and PTH (rs694, rs6256 and rs307247) through real-time PCR. The data were submitted to statistical analysis with a significance level of 0.05. In the MD dimension, the sex, dental group and dental arch were associated with variation in TCS (P < .05). In the BL dimension, the sex, dental group, dental arch and polymorphism in rs694 and rs307247 were associated with variation in TCS. In short, this study suggests that genetic polymorphisms of PTH are associated with variations in the BL TCS of permanent human teeth.

Genetic polymorphisms are involved in oral health-related quality of life in skeletal class III patients submitted to orthognathic surgery.

This study aimed to evaluate whether sex and genetic polymorphisms impact the oral health-related quality of life (OHRQoL) preoperatively and the difference between preoperative and postoperative OHRQoL in skeletal Class III patients submitted to orthognathic surgery. This longitudinal study consisted of ninety-nine patients with skeletal Class III malocclusion who required orthognathic surgery. The Oral Health Impact Profile-14 (OHIP-14) is a questionnaire used to assess the OHRQoL with a 5-point Likert-type scale, covering seven domains related to physical and psychosocial factors. The questionnaire was applied in the preoperative and postoperative periods, and the difference scores were calculated to assess the OHRQoL after orthognathic surgery. The DNA was extracted from oral mucosa cells to evaluate genetic polymorphisms in ANKK1, DRD2, ESR1, and ESR2 through real-time PCR. There was an improvement in all OHRQoL domains following orthognathic surgery (p < 0.05). In the preoperative evaluation, women presented worse OHRQoL (p < 0.05) than men. There was no statistical difference between sex and the OHRQoL after surgery (p > 0.05). When evaluating the polymorphisms and preoperative OHIP-14 scores, CT genotype patients for rs1800497 (ANKK1) had a worse perception of the physical pain domain than CC genotype (p = 0.026), and CC genotype patients for rs1256049 (ESR2) had a worse perception of the functional limitation domain than CT genotype (p = 0.002). In the analysis between polymorphisms and postoperative and preoperative difference scores, CT genotype patients for rs1256049 (ESR2) had a greater improvement in the perception of the physical pain domain than the CC genotype (p = 0.031). In rs6275 and rs6276 (DRD2), patients with the CC genotype worsened the perception of the functional limitation domain than the TT genotype (p = 0.045), and AA genotype patients worsened the perception of the functional limitation domain than GG genotype (p = 0.048) after surgery, respectively. In addition, patients with the CT genotype for rs1800497 (ANKK1) had a greater improvement of OHRQoL perception in the total scale than the TT genotype (p = 0.018), and CT genotype patients had a greater improvement in the perception of function limitation domain than TT genotype (p = 0.017). Women have a worse perception of OHRQoL in the preoperative period of orthognathic surgery. Furthermore, polymorphisms in the ANKK1, DRD2, and ESR2 genes could be involved with OHRQoL in the preoperative period and following orthognathic surgery. The knowledge of the genetic background concerning OHRQoL in skeletal class III patients would aid in clinical practice to screen for associated genetic factors and prevent OHRQoL deterioration, especially after orthognathic surgery, considering that patients' genetic profiles would soon be available.

Estrogen Receptor-β Gene Cytosine-Adenine (ESR2-CA) Repeat Polymorphism in Postmenopausal Colon Cancer

The pathobiological role of estrogen is controversial in colorectal cancer. Cytosine-adenine (CA) repeat in the estrogen receptor (ER)-β gene (ESR2-CA) is a microsatellite, as well as representative of ESR2 polymorphism. Though its function is unknown, we previously showed that a shorter allele (germline) increased the risk of colon cancer in older women, whereas it decreased it in younger postmenopausal women. ESR2-CA and ER-β expressions were examined in cancerous (Ca) and non-cancerous (NonCa) tissue pairs from 114 postmenopausal women, and comparisons were made considering tissue types, age/locus, and the mismatch repair protein (MMR) status. ESR2-CA repeats <22/≥22 were designated as 'S'/'L', respectively, resulting in genotypes SS/nSS (=SL&LL). In NonCa, the rate of the SS genotype and ER-β expression level were significantly higher in right-sided cases of women ≥70 (≥70Rt) than in those in the others. A decreased ER-β expression in Ca compared with NonCa was observed in proficient-MMR, but not in deficient-MMR. In NonCa, but not in Ca, ER-β expression was significantly higher in SS than in nSS. ≥70Rt cases were characterized by NonCa with a high rate of SS genotype or high ER-β expression. The germline ESR2-CA genotype and resulting ER-β expression were considered to affect the clinical characteristics (age/locus/MMR status) of colon cancer, supporting our previous findings.

Association of ESR1 gene polymorphisms with the susceptibility to Hepatitis B virus infection and the clinical outcomes.

Estrogen receptor alpha (ESR1) has been implicated in the pathological process of Hepatitis B virus (HBV) infection and is probably an important determinant for gender differences. In this study, a total of 975 subjects including 368 healthy controls, 323 hepatocellular carcinoma (HCC) patients with HBsAg positive, and 284 HBV-infected subjects without HCC were included. Three single nucleotide polymorphisms of ESR1 (rs2234693, rs2077647, rs2228480) were detected to investigate the correlation between ESR1 polymorphisms and the susceptibility to HBV persistence and the clinical outcomes. The association of ESR1 polymorphisms with HCC prognosis was investigated in our cohort enrolling 376 HBV-HCC patients. The frequency of rs2234693 C allele was lower in chronic Hepatitis B (CHB) and liver cirrhosis(LC) than that in HCC patients in the males (adjusted odds ratio [AOR] = 0.63, 95% confidence interval [CI] = 0.41-0.96). rs2228480 A allele was associated with increased risk of LC (AOR = 2.20, 95%CI = 1.06-4.56) in HBV genotype C, and significantly decreased the risk of HCC recurrence (p = 0.010) and ESR1 mRNA level in tumor tissues (p = 0.032). Haplotype C-G-G was associated with significantly increased risk of HBV persistence (OR = 1.37, 95%CI = 1.08-1.73), while it was opposite for C-A-G and T-G-G (OR = 0.41, 95%CI = 0.27-0.62; OR = 0.53, 95%CI = 0.32-0.85, respectively). These results imply that combinations of these ESR1 polymorphisms may be valuable for the prediction of HBV persistence.