ESR1 Gene 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

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.

PP156 Link of ESR1 gene polymorphisms with breast cancer risk in Bangladeshi women

PP156 Link of ESR1 gene polymorphisms with breast cancer risk in Bangladeshi women

Evaluation of Comt2, Comt3, Cyp1b1, and Esr1 gene polymorphisms as risk factor for endometrial polyp

ABSTRACT The aim of this study is to evaluate COMT2, COMT3, CYP1B1, and ESR1 gene polymorphisms and occurrence of endometrial polyps. In addition, we intended to evaluate the clinical and epidemiological features of patients with and without the presence of the disease, characterizing the possible risk factors. A cross-sectional study was performed, with a total of 309 women, including 236 in the group of women with endometrial polyp confirmed by hysteroscopy and anatomical pathological examination and 73 in the group of people with diagnostic hysteroscopy without abnormal findings from the macroscopic point of view. Polymorphisms of four genes were studied: COMT2 (rs4680), COMT3 (rs5031015), CYP1B1 (rs1056836), and ESR1 (rs2234693). Polymorphism genotyping was determined using real-time polymerase chain reaction. Considering the results, no differences were identified between the two groups with respect to age, body mass index, diabetes, dyslipidemia, or smoking. The group of women without endometrial polyps showed higher use of hormone therapy than the other group (16.4 percent versus 3.8 percent, p < .001). The COMT2, COMT3, CYP1B1, and ESR1 genes exhibited no significant difference for the occurrence of endometrial polyp between the two groups. The research concluded that no correlation was identified between the genetic polymorphisms evaluated and the presence of endometrial polyps.

Search for associations of bull sperm quality with &lt;i&gt;ESR1&lt;/i&gt; gene polymorphism

Materials and methods. The semen of 53 bulls was collected at OJSC Nevskoe. A total of 110 bull semen samples were analyzed. Sperm quality was determined using Argus-CASA (ArgusSoft, Russia). Membrane integrity was determined by staining the samples with nigrosine-eosin dye (Diam, Russia) and a Motic BA 410 microscope. Spermatozoa respiration was determined using an Expert-001 instrument. The functional state of the energy system was assessed by the reaction of respiration to the addition of the uncoupler of respiration and phosphorylation, 2,4 dinitrophenol (2,4-DNF). DNA for genetic analysis was isolated from semen by the phenol-chloroform method. Sanger sequencing was performed on an Applied Biosystems 3500 Genetic Analyzer using commercial BigDye® Terminator v3.1 Sequencing Standard Kits (Applied Biosystems) according to the manufacturer's protocol.Results. Sperm quality were characterized by high individual variability. Thus, the volume of the ejaculate was from 2 to 15 ml, the concentration of spermatozoa was from 0.6 to 1.7 billion/ml, the total number of spermatozoa in the ejaculate was from 1.6 to 15 billion, and progressive motility was from 0 to 85%. Four SNPs were identified for the ESR1 gene. No significant associations of ESR1 gene polymorphism were found, except for a significant association of ESR1 665 G&gt;C with spermatozoa concentration and the number of swollen acrosomes

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.

The influence of ESR1 polymorphisms on selected hormonal, metabolic and mineral balance markers in women with hyperandrogenism

Hyperandrogenism is the most common endocrine disorder in women, characterized by an imbalance in normal estrogen and androgen levels in the blood. Androgens influence bone mineral density, body mass composition, muscle mass, mental state, and the regulation of sexual function.. The aim of the study was to assess the effect of estrogen receptor α gene (ESR1) polymorphisms on selected markers of bone metabolism and hormonal parameters in women with hyperandrogenism. The study group included 80 young women with hyperandrogenism who underwent measurements of bone mineral density (BMD), and determination of hormonal and metabolic parameters. Enzyme immunoassays were used to measure leptin, sRANKL (soluble receptor activator of nuclear factor-kB ligand), osteoprotegerin and 25-OH vitamin D total levels. An analysis of ESR1 gene polymorphisms was performed using the real-time PCR method. A relationship was demonstrated between the concentration of free estradiol (FEI) and the concentration of 17-OH-progesterone, and the ESR1 gene polymorphisms: rs3020314 (p = 0.031, p = 0.026 respectively) and rs1884051 (p = 0.033, p = 0.026 respectively). In conclusion, the ESR gene polymorphisms may be associated with hormonal disturbances in the concentration of estrogens and androgens, in hyperandrogenism in young women which may indirectly affect bone mineral density. However, no statistically significant relationships between the studied polymorphisms and the selected parameters of mineral metabolism have been demonstrated..

GENETIC ASPECTS OF ADVERSE CONSEQUENCES OF PREGNANCY WITH ISTHMIC-CERVINAL INSUFFICIENCY

According to modern ideas, both physiological and pathological processes are the result of complex interactions of genetic and epigenetic factors. Among the publications of recent years, there are no studies on the connection of PROGINS and ESR1 gene polymorphisms or gene methylation with ICI and adverse pregnancy outcomes on its background, which prompted us to conduct research in this direction.&#x0D; The aim of the study. To assess the influence of genetic and eugenetic factors on adverse pregnancy outcomes in isthmic-cervical insufficiency (ICI).&#x0D; Research material and methods. comprehensively examined 20 pregnant women with ICI, the correction of which was carried out with the use of a cerclage (main group), in which 2 subgroups were distinguished: ICI1 - 10 women with ICI and an unfavorable end of pregnancy (miscarriage before 22 weeks of pregnancy in 4 women and premature birth in 6 patients ) and ICI2 – 20 patients in whom delivery was urgent (after 37 weeks).&#x0D; A molecular genetic analysis of PGR gene variants (Alu insertion), ESR1 (A351G, rs 9340799) and an epigenetic study of methylation of the promoter region of the estrogen receptor α (ESR1) gene was performed.&#x0D; The results. Loss of pregnancy and premature birth in ICI can be caused not only by a decrease in hormone levels, but also by a violation of hormonalreceptive relationships. The probability of genetic conditioning of disorders of receptive progesterone and estrogen mechanisms in patients with ICI has been established. The presence in a pregnant woman of the mutant T2 allele of the PGR polymorphism (Alu-insertion) and the combination of homozygous genotypes T2T2+ GG of the polymorphic variants of the PGR (Alu-insertion) and ESR1 (A351G rs9340799) genes can be markers of a high risk of adverse pregnancy termination in ICI. In addition, the change in gene expression can be caused by epigenetic disorders, namely gene methylation: hypermethylation of the promoter region of the estrogen receptor α (ESR1) gene was detected in 40% of women with ICI and pregnancy loss in the II trimester or premature birth, which is 4 times higher than the rate women with ICI and normal termination of pregnancy.&#x0D; Conclusions. Adverse pregnancy outcomes with ICI can be caused by genetic (presence of a mutant T2 allele of the PGR polymorphism and combinations of homozygous T2T2+ GG genotypes of polymorphic variants of the PGR Alu-insertion and ESR1 A351G genes) and epigenetic factors (hypermethylation of the promoter region of the estrogen receptor α ESR1 gene). However, these results are preliminary and require further indepth studies on larger data samples.

The role of CYP19A1 and ESR2 gene polymorphisms in female androgenetic alopecia in the Polish population.

IntroductionAndrogenetic alopecia is the most common type of non-cicatricial alopecia both in male and female patients. The mechanism that leads to hair loss is similar in both sexes, but the underlying cause, and especially the role of genes and sex hormones in the pathogenesis of the disease in women has not fully been explained as of yet. So far, a few attempts have been made to assess selected SNPs for CYP19A1 and ESR2 genes, but their results are not unequivocal and fully reproducible.AimTo investigate the association of 13 CYP19A1 and 11 ESR2 gene SNPs with female androgenetic alopecia (FAGA) in a population of Polish patients, including some already genotyped SNPs of possible importance for FAGA pathophysiology in other populations.Material and methodsTwenty-four genetic polymorphisms were analysed for the ESR2 and CYP19A1 genes in 117 patients with FAGA and 128 healthy subjects treated at the Department of Dermatology in Krakow.ResultsIn the studied Polish population, none of the selected SNPs, frequently detected in the Caucasian population and linked with the transformation pathway of sex hormones, showed a significant association with FAGA.ConclusionsFurther studies into the genetic background of androgenetic alopecia are needed. Ethnic differences as well as the size of the studied population may be of great significance for the obtained results.

Роль генов ESR1 эстрогеновых и PRG прогестероновых рецепторов в развитии доброкачественной дисплазии молочных желез у женщин репродуктивного возраста с гиперплазией эндометрия

Study Objective: To identify the role of estrogen (ESR1) and progesterone (PRG) receptor genes in benign mammary dysplasia (BMD) in women of reproductive age with endometrial hyperplasia (EH). Study Design: prospective controlled cohort study. Materials and Methods. We examined 105 women aged 18 to 49 years old who were divided into three groups: group I — 36 BMD patients; group II — 27 women with EH without atypia; and group III — 42 BMD patients with EH without atypia. Patients with mammary disorders were divided into subgroups of diffuse and nodal BMD. We studied polymorphism of estrogen (ESR1) and progesterone (PRG) receptor genes and the ratio of their isoforms in blood serum. ESR1 and PRG gene polymorphism was analysed using polymerase chain reaction with fluorescent genotyping detection with TaqMan probes. Study Results. In PvuII C/T polymorphism of ESR1 gene there were significant differences between women with diffuse and nodal BMD in СС allele (p = 0.014), but not between study groups. Analysis of the rate of Xbal A/G alleles of ESR1 gene revealed significant differences between group I and group III in GG allele (p = 0.015), while there were no differences between women with diffuse and nodal BMD. The rate of polymorphism in Val660Leu and +331G/A alleles of PRG gene was not statistically significant in study groups; also, there were no statistically significant differences in diffuse and nodal BMD. Conclusion. Combined hyperplastic processes in endometrium and mammary glands depend on the specificity in the polymorphism system of estrogen and progesteron receptor genes. Associations between various combinations of susceptibility genes demonstrate the presence of specificity for each clinical and pathogenic variant of BMD (diffuse or local forms). Keywords: benign mammary dysplasia; endometrium hyperplasia; estrogen receptors; progesterone receptors; ESR1, PRG gene polymorphism

Effect of estrogen receptor gene ESR1 polymorphism on development of premenstrual syndrome

To identify risks of development of any disease is a priority of modern medicine. The aim of this study was to investigate the frequency of polymorphic variants of A-351G gene estrogen receptor ESR1 in patients with various forms of PMS. Molecular genetic analysis of ESR1 gene polymorphism in 50 women with PMS (25 women of them had edematous form of disease, 25 – neuropsychical, 25 – mild, 25 – severe form) was carried out. 25 women without diagnosis of PMS were examined as controls. The study A-351G polymorphism estrogen gene ESR1 showed no statistically significant differences in the frequency of distribution of gen-otypes and alleles between women with PMS and without this pathology. However, the frequency of GG genotype in women with severe PMS was significantly higher in 8.0 times compared with healthy women (χ2=4.87, p=0.03) and in women with edematous form of PMS – in 7.0 times (χ2=3.72, p=0.05). Thus, a polymorphic variant of A-351G gene ESR1 estrogen can be considered as a marker of PMS. Pathologi-cal variant GG genotype was significantly associated with the presence of edematous and severe forms of the disease.

The AGT Haplotype of the ESR2 Gene Containing the Polymorphisms rs2077647A, rs4986938G, and rs1256049T Increases the Susceptibility of Unexplained Recurrent Spontaneous Abortion in Women in the Chinese Hui Population.

BackgroundEstrogen has an important role in unexplained recurrent spontaneous abortion (URSA). Polymorphisms of the ESR1 gene and the ESR2 gene have been identified as risk factors for URSA, but with varied associations in Chinese populations. This study aimed to compare the role of gene polymorphisms of ESR1 and ESR2 and the risk of URSA in the Chinese Hui and Chinese Han populations.Material/MethodsChinese Hui women (n=171) and Chinese Han women (n=234) with URSA were compared with healthy controls (n=417) matched by ethnicity and age. Genotyping was performed using direct sequencing and identified three polymorphisms of the ESR1 gene (rs9340799, rs2234693, and rs3798759) and three polymorphisms of the ESR2 gene (rs207764, rs4986938, and rs1256049). The association between ESR1 and ESR2 gene polymorphisms and the risk of URSA was evaluated statistically using the odds ratio (OR) and 95% confidence interval (CI).ResultsNo association was detected between the allelic, dominant, and recessive models of ESR1 and ESR2 gene polymorphisms and the risk of URSA in Chinese Han and Hui populations (p>0.05). The distribution of the AGT haplotype containing ESR2 gene polymorphisms rs2077647A, rs4986938G, and rs1256049T was significantly reduced in patients with URSA compared with controls in the Chinese Hui population (OR, 0.29; 95% CI, 0.14–0.62; p=0.0009; padj=0.005).ConclusionsThe AGT haplotype of the ESR2 gene containing the polymorphism rs2077647A, rs4986938G, and rs1256049T (ESR2 hapAGT) was a protective factor for URSA in women in the Chinese Hui population when compared with the Chinese Han population.

ESTRADIOL BLOOD LEVEL AND ESR1 GENE POLYMORPHISM IN WOMEN WITH PREMENSTRUAL SYNDROME

The aim: To evaluate the association between estrogen receptor (ESR1) α- Xbal polymorphism with estradiol serum blood level in the patients with premenstrual syndrome. Materials and methods: 50 women with premenstrual syndrome and 20 controls were examined. The level of estradiol was measured in the blood serum in both phases of the menstrual cycle by ELISA method. Polymerase chain reaction was used to study ESR1 gene polymorphism (A-351G variant). Results: The estradiol concentration was similar in two phases of the menstrual cycle between healthy women and patients with premenstrual syndrome. But the more growth of estradiol in the luteal phase was determined in the persons with premenstrual syndrome. The rate of GG genotype was the largest in women with severe premenstrual syndrome (χ2=3.52, p=0.06). Also, in the persons with severe premenstrual syndrome who had G allele (GG+AG genotype) the estradiol concentration in the luteal phase of the menstrual cycle was on 50.00 % (p=0.02) higher compared to carriers of AA genotype. There was no difference in estradiol level between healthy women with GG+AG genotype and AA genotype. Conclusions: AG polymorphism of ESR1 gene may be the marker of development of premenstrual syndrome.

Полиморфизм гена ESR1 ассоциирован с возрастом менархе у женщин России

Полиморфизм гена ESR1 ассоциирован с возрастом менархе у женщин России

Influence of Estrogen Receptor Alpha Polymorphism on Bone Mineral Density in Iranian Children

Background: Bone mass acquisition in childhood is directly linked to adult bone mineral density (BMD) and fracture risk. BMD is a heritable trait, more than 70% of its variability among a population is affected by genetic factors. Objectives: In the present study, we wanted to investigate the association between estrogen receptor alpha (ESR1) polymorphisms, PvuII (rs2234693) and XbaI (rs9340799), and bone area, bone mineral content (BMC), and BMD of the lumbar spine, femoral neck, and also of the total body less the head in Iranian children. Methods: The ESR1 gene PvuII and XbaI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Bone area, BMC, BMD, and bone mineral apparent density (BMAD) were assessed by dual-energy X-ray absorptiometry (DEXA). Linear regression was carried out to examine the effects of the ESR1 (PvuII and XbaI) polymorphisms on DEXA outputs when adjusted for confounding factors (i.e., age, sex, BMI, and pubertal stage) in 3 models. Results: ESR1 (PvuII) gene polymorphisms (CT vs. CC) showed significant effects on the BMC of the total body less the head in all 3 models. For ESR1 (XbaI), individuals with the AG genotype had higher lumbar spine BMD and lumbar spine BMAD compared to other genotypes. Conclusions: It seems that the PvuII and XbaI polymorphisms of ESR1 could be associated with BMC and BMD variation in Iranian children and adolescents.

A7233 Polymorphism and m RNA expression of The Estrogen Receptor alpha gene in Coronary Artery Disease- A study from India

Objectives: To study the role of −397T > C ESR1 polymorphism in CAD in the north Indian population. We hypothesized that ESR1 gene polymorphism may influence the susceptibility to CAD through variation in ERα expression. In order to assess the veracity of this concept, we evaluated ERα m RNA expression in peripheral blood leucocytes of our cohort of CAD patients. Methods: 100 clinically confirmed CAD patients and normal healthy controls were included in this study. DNA and RNA from both CAD patients and healthy controls was extracted using Gene Aid DNA extraction kit and trizol RNA isolation method. We employed PCR-RFLP technique to characterize −397 T > C ESR1 gene polymorphism. Quantitative Real Time was carried out for measurement of ESR α expression on a Rotor-Gene Instrument. Results: The frequency of −397T > C ESR1 SNP of mutant homozygous (CC) plus heterozygous (TC) genotype was higher (78% vs 49%) in CAD as compared to control subjects (p < 0.0001. Moreover the ESR1 m RNA expression was highest in CAD patients with wild type homozygous TT genotype (2-Δct = 0.28) as compared to homozygous CC genotype (2-Δct = 0.09), and intermediate expression level in heterozygous TC genotypes (2-Δct = 0.14) subgroups of CAD patients. As compared to wild type TT genotype taken as reference, the fall in TC genotype (2.02 fold) and CC genotype (2.96 fold), was statistically significant (p = 0.001 and 0.008 respectively). Conclusion: Our data associates significant involvement of ESR1 polymorphism genotypes with under expression of its mRNA which consequently results in high-risk of developing CAD. However, further research is warranted on the differences of these functional polymorphisms and their impact on ESR1 gene expression and their correlation with the development of CAD.

Role of genetic factors in the development of premenstrul syndrome

To identify risks of development of any disease is a priority of modern medicine. The article deals with ESR1 gene polymorphisms and its role in the development of premenstrual. The objective: of this study was to investigate the frequency of polymorphic variants of A-351G gene estrogen receptor ESR1 in patients with various forms of premenstrual syndrome. Materials and methods. Molecular genetic analysis of ESR1 gene polymorphism was determines in 50 women with premenstrual syndrome (25 women of them had edematous form of disease, 25 – neuropsychical one; 25 suffered from mild form, 25 – severe one). 25 women without diagnosis of premenstrual syndrome were examined as controls. Results. The study of A-351G polymorphism estrogen gene ESR1 demonstrated no statistically significant differences in the frequency of distribution of genotypes and alleles between women with premenstrual syndrome and without this pathology. However, the frequency of GG genotype in women with severe PMS was significantly higher in 8.0 times compared with healthy women (χ2=4.87; p=0.03) and in women with edematous form of PMS – in 7.0 times (χ2=3.72; p=0.05). Conclusion. Thus, a polymorphic variant of A-351G estrogen receptor gene ESR1 can be regarded as a marker for the development of premenstrual syndrome. Pathological variant GG genotype is significantly associated with the presence of edematous and severe forms of the disease. Key words: premenstrual syndrome, genetic factors, development.

Associations of ESR1 and ESR2 gene polymorphisms with metabolic syndrome and its components in postmenopausal women

ObjectivesMetabolic syndrome (MS) affects a quarter of Polish people and is associated with diabetes mellitus type 2 and ischemic heart disease. The prevalence of MS in postmenopausal women can be increased by the lack of protective effects of oestrogens. In the near future, because of the general increase in life expectancy, the number of postmenopausal women will rise substantially. Therefore, investigating both the environmental and the genetic factors predisposing to MS may have a great impact on women’s health. The aim of this study was to determine whether particular oestrogen receptor (ESR) gene polymorphisms can predispose to the development of MS in women after menopause. Study designThe sample consisted of 147 postmenopausal women. In addition to collecting medical history and analyzing body composition using the TANITA scale, patient’s waist size, blood pressure, serum lipids, glucose, insulin, C-reactive protein and adiponectin were measured. The analysis of ESR gene polymorphisms was performed using the Sequenom MassARRAY platform. ResultsThree out of ten analyzed polymorphisms in the ESR1 gene (rs2234693, rs6902771, rs7774230) and one out of eight analyzed polymorphisms in the ESR2 gene (rs3020449) were associated with MS. The ESR1 rs2234693, rs6902771 and rs7774230 polymorphisms were associated with serum concentrations of high-density lipoproteins. The ESR2 rs3020449 polymorphism was associated with serum concentrations of total cholesterol and low-density lipoprotein. Four ESR1 polymorphisms (rs1709183, rs2234693, rs6902771, rs7774230) were associated with total fat tissue content. ConclusionsBearing the particular alleles at the ESR gene polymorphisms may impact the development of MS and some of the ESR polymorphisms may influence serum cholesterol concentrations in women after menopause.

Полиморфизм генов эстрогеновых рецепторов первого типа и сосудисто-эндотелиального фактора роста как предиктор особенностей течения синдрома гиперстимуляции яичников в программе экстракорпорального оплодотворения

Полиморфизм генов эстрогеновых рецепторов первого типа и сосудисто-эндотелиального фактора роста как предиктор особенностей течения синдрома гиперстимуляции яичников в программе экстракорпорального оплодотворения

Interaction of estrogen receptor β and negative life events in susceptibility to major depressive disorder in a Chinese Han female population

BackgroundBoth genetic and environmental factors as well as their interaction contribute to the etiology of major depressive disorder (MDD). Estrogen receptor β (ESR2) may play a vital role in the development of MDD in females. The aim of this study is to analyze ESR2 gene polymorphisms and the interaction of ESR2 gene variation and negative life events concerning the risk of developing MDD in females, especially during menopausal stage. MethodsGenotyping was performed by Taqman allelic discrimination assay among 191 female MDD patients and 200 healthy females. Life Events Scale and the generalized multifactor dimensionality reduction method were employed to assess the frequency and severity of negative life events and gene-environment interaction (G×E), respectively. All subjects were regrouped into reproductive and menopausal group based on age. Logistic regression was used to evaluate the set of risk factors. ResultsNo association of ESR2 G×E interaction with MDD was found in the reproductive group. However, in menopausal females, significant G×E interactions between negative life events and allelic variation of rs1256049 and rs4986938 were observed. Individuals with the A+ allele of rs1256049 and rs4986938 were susceptible to MDD when exposed to low negative life events. LimitationAssessment of negative life events was influenced by subjective interpretation. ConclusionsESR2 may modify the interaction between negative life events and MDD in the Chinese Han menopausal females. To our knowledge, this study is the first to report an effect modification between negative life events and ESR2 variations in female MDD patients.