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

Abstract

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.

The neuroprotective effect of 17β-estradiol is independent of its antioxidative properties

“…The deletion of ERα in knockout mice completely abolishes the protective effects of E 2 , while the protection against ischemic brain injury is totally preserved in the absence of ERβ. This is also supported by a recent metaanalysis showing that patients carrying loss-of-function mutations of ERα receptor have more severe ischemic brain damage stroke patients (Li et al, 2012). This is in line with other results showing that neuroprotection involves attenuation of NADPH oxidase activation and superoxide production via an ERα-mediated nongenomic signaling cascade (Zhang et al, 2009).…”

Brain volumes in late life: gender, hormone treatment, and estrogen receptor variants

“…Previous studies have reported significant associations between these SNPs and brain-related disorders, including cognitive impairment a d Alzhei er's disease (www.alzgene.org) Ancelin, 2012, Sundermann et al, 2010), as well as cholesterol levels and cardiovascular disease (Li et al, 2012, Rexrode et al, 2007. There is also some evidence that they may be functionally significant (Alonso et al, 2011, Maruyama et al, 2000.…”

“…Associations with cardiovascular disease and ischemic stroke have also been reported (Li et al, 2012, Rexrode et al, 2007. To date however, only three studies have investigated potential associations between ESR gene variants and brain volumes, one of which was a study of neonates (Knickmeyer et al, 2013).…”

ESR1 gene polymorphisms PvuII (rs2234693T>C) and XbaI (rs9340799A>G) may not be directly correlated with cardiovascular disease risk

“…Consequently, early diagnosis and prevention are critical for disease management. Recent studies have shown that estrogen-related genes are associated with a significantly increased risk of CVD (Li et al, 2012).…”