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% CI s) 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.
雌激素受体1基因多态性与复发性自然流产风险的Meta分析摘要背景：雌激素是一种重要的生殖甾体激素，在妊娠建立与维持中具有重要作用，其生物学效应主要是由雌激素受体1(ESR1) 介导的。研究证实ESR1基因多态性与复发性自然流产（RSA）有关，但两者间关系仍存在争议。本研究旨在通过Meta分析阐明ESR1 PvuII (-397 C/ T，rs2234693) 和XbaI (-351 A/ G，rs9340799) 多态性与RSA风险的相关性，以期进一步阐释ESR1基因多态性在RSA发病中的作用，为进一步探索RSA发病机制及临床诊断与治疗提供科学依据。 方法：本研究纳入的文章为截止到2018年1月3日检索自Pubmed、Embase、Cochrane Library、中国知网和万方医学在线数据库的文献，运用STATA 12.0软件进行数据处理，并采用固定效应 (FEM)/随机效应模型 (REM) 计算比值比 (ORs) 和95%可信区间 (95% CIs)。 结果：共纳入7篇病例对照研究，包括836例复发性自然流产病例和1164名正常生育妇女对照。Meta分析结果表明，对于任何一种遗传分析模型来说，ESR1多态性与RSA发病风险均不相关。然而，对不同地域进行亚组分析发现，对于rs9340799多态性来说，在非亚洲组中纯合遗传模型 (OR = 2.40，95% CI = 1.05-5.50，P = 0.039) 显示与RSA风险增加显著相关; 此外，在亚洲组中杂合遗传模型 (OR = 0.53，95% CI = 0.33-0.85，P = 0.009) 和显性遗传模型 (OR = 0.55，95% CI = 0.30-0.98，P = 0.042) 与RSA风险降低相关。 结论：总的来说，ESR1基因多态性与RSA风险无明显相关。然而，亚组分析表明ESR1 rs9340799多态性与非亚洲人RSA风险增加相关，而与亚洲人RSA风险降低相关，提示种族遗传差异可能是影响ESR1基因多态性与RSA风险的因素，但仍需扩大样本进一步证实。.
Keywords: Estrogen Receptor 1; Meta-Analysis; Polymorphism; Recurrent Spontaneous Abortion; Risk.