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

Abstract

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

Pvuii (Rs2234693) Polymorphism of the Estrogen Receptor Alpha Gene in Women From Sumy Oblast, Ukraine, With Endometrial Hyperplastic Process

“…However, many scientists demonstrated in their studies that the PvuII polymorphism of the ESR1 gene was associated with numerous diseases, such as hypertension, dyslipidemia, coronary atherosclerosis [10], type II diabetes [31,32], sexual dysfunctions [33], lung cancer [34], coronary artery disease [35], osteoarthritis [36], osteoporosis [37], precocious puberty [38], repeated spontaneous abortions [39], chronic hepatitis B [40], systemic lupus erythematosus [41,42], Alzheimer's disease [43], dementia [44], prostate cancer in men [45]. Genetic variation T/C of the PvuII polymorphism of the ESR1 gene may be a risk factor for hepatocellular carcinoma, gallbladder cancer [46], breast cancer [10,47], and endometrial cancer [48].…”

Comprehensive analysis of the differential expression profile of microRNAs in missed abortion

“…However, impaired trophoblast cell proliferation and migration correlated with the downregulation of the Wnt/β‐catenin signaling pathway that led to the unexplained recurrent spontaneous abortion . Additionally, ESR1 , which is involved in the estrogen signaling pathway, and its genetic polymorphisms are associated with the recurrent spontaneous abortion risk . ESR1 mRNA expression might be regulated by hsa‐miR‐361‐3p in our study.…”

Research progress of immune balance and genetic polymorphism in unexplained recurrent abortion

“…The physiological function of estrogen is mediated by two estrogen receptors, namely estrogen receptor 1 (ESR1) and ESR2, which are expressed in various tissues of the female reproductive system. Studies have shown that estrogen receptors may induce immune tolerance at the maternal-infant interface, indicating that ESR is a key factor in the pathogenesis of URSA [134,135].…”

“…For Asians, ESR1 rs9340799(-351A/G) polymorphism may reduce the risk of RSA, while for non-Asians it may increase the risk. Tang et al [135] found that ESR1 gene polymorphisms rs9340799, rs2234693, and rs3798759 were not related to URSA in Chinese Han and Hui populations. Another study conducted on Tunisian and Egyptian women showed there was a significant association between the ESR1 variant and the increased risk of RSA [137,138].…”