Association between estrogen receptor alpha c.454-397T>C and c.454-351A>G and ischemic stroke risk: a systematic review and meta-analysis

The association between estrogen receptor alpha (ESR1) c.454-397T>C and c.454-351A>G polymorphism and ischemic stroke remains controversial. The aim of this study was to perform a meta-analysis to investigate a more authentic association between c.454-397T>C and c.454-351A>G mutation and ischemic stroke. Systematic searches of electronic databases Embase, PubMed, Web of Science as well as hand-searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95?% confidence intervals (95?% CIs) were performed. Different effect models were used according to the difference in heterogeneity. Publication bias was tested by Begg's funnel plot and Egger's regression test. For c.454-397T>C mutation, five studies were combined. Significant association was found in allelic model (OR?=?1.12, 95?% CI?=?1.01-1.25, p?=?0.03), additive model (OR?=?1.25, 95?% CI?=?1.01-1.54, p?=?0.04), and recessive model (OR?=?1.23, 95?% CI?=?1.02-1.49, p?=?0.03), whereas no evidence of association was found for dominant model (OR?=?1.10, 95?% CI?=?0.85-1.42, p?=?0.47). For c.454-351A>G mutation, no evidence of association was found for all genetic models. Our meta-analysis suggests that ESR1 c.454-397T>C mutation is significantly associated with increased risk of ischemic stroke, whereas no evidence of association was found for ESR1 c.454-351A>G mutation.