Association between Common Genetic Variants in ESR1 and Stroke Risk: A Systematic Review and Meta-Analysis

The associations between estrogen receptor alpha (ESR1) polymorphisms and stroke risk have been investigated in various studies, but remain controversial. The aim of this meta-analysis was to determine the relationships between ESR1 rs2234693 and rs9340799 polymorphisms and the risk of stroke.

Electronic databases of PubMed, Embase, Cochrane Library, CNKI, VIP database, and WanFang database were searched for eligible studies up to March 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of associations under different genetic models.

Ten independent case-control studies including 2151 stroke cases and 6378 control subjects were enrolled in this meta-analysis. The meta-analysis results indicated that ESR1 rs2234693 polymorphism was associated with an increased risk of stroke in recessive model (OR, 1.20; 95%CI, 1.04-1.38) and homozygous model (OR, 1.18; 95%CI, 1.00-1.38). Subgroup analysis on stroke subtype showed that rs2234693 polymorphism was connected with ischemic stroke, but not hemorrhagic stroke. The further subgroup analyses on ethnicity and gender suggested that the association between rs2234693 polymorphism and stroke risk was significant in Caucasian population and in the male population. No positive associations between rs9340799 polymorphism and stroke risk were detected in 4 genetic models.

The results of this meta-analysis suggest that ESR1 rs2234693 polymorphism is significantly correlated with an increased risk of stroke, especially ischemic stroke. There was no evidence of a significant association between ESR1 rs9340799 polymorphism and stroke risk.