Association between Lys198Asn polymorphism of endothelin-1 gene and ischemic stroke: A meta-analysis

Abstract

Background: Endothelin (ET)-1 is a potent vasoconstrictor peptide produced by endothelial cells and associated with vascular dysfunction and cardiovascular disease. Lys198Asn is a single-nucleotide polymorphism (SNP) of gene encoding ET-1 (EDN1). It is hypothesized that it might have a role in altering ET-1 and ultimately leading to vascular dysfunction and ischemic stroke. We therefore conducted a meta-analysis to investigate the association between Lys198Asn polymorphism of EDN1 gene and susceptibility of ischemic stroke.

Methods: This meta-analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed, Google Scholar, Embase, Web of Science, J-STAGE, and China National Knowledge Infrastructure (CNKI) for relevant studies. The association between Lys198Asn polymorphism and ischemic stroke susceptibility was evaluated by calculating the pooled ORs and 95% CIs.

Results: Our analysis included 1,291 cases and 2,513 controls. Meta-analysis established a significant association between Lys198Asn SNP of EDN1 gene and ischemic stroke when assuming either recessive model (OR: 1.30; 95% CI: 1.02-1.65; p = .03; I² = 41%) or dominant model (OR: 1.48; 95% CI: 1.24-1.76; p < .001; I² = 61%). There was no evidence of publication bias in either of the recessive model (Egger test: p = .23; Begg test: p = .85) or dominant model (Egger test: p = .79; Begg test: p = .85). A subgroup analysis based on subtypes of ischemic stroke showed that Lys198Asn SNP was only associated with large vessel infarction but not with lacunar infarction caused by small vessel disease. A subgroup analysis based on ethnicity revealed that the Lys198Asn polymorphism of the EDN1 gene was associated with ischemic stroke only in Caucasians.

Conclusions: The present meta-analysis suggests that Lys198Asn polymorphism of EDN1 gene is associated with an increased risk for ischemic stroke.

Keywords: EDN1; K198N; Lys198Asn; cerebral infarction; endothelin-1; ischemic stroke; rs5370.