Abstract
BackgroundEndothelin (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.MethodsThis 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.ResultsOur 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; I 2 = 41%) or dominant model (OR: 1.48; 95% CI: 1.24–1.76; p < .001; I 2 = 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.ConclusionsThe present meta‐analysis suggests that Lys198Asn polymorphism of EDN1 gene is associated with an increased risk for ischemic stroke.
Highlights
Endothelin (ET)‐1 is a potent vasoconstrictor peptide produced by en‐ dothelial cells and associated with vascular dysfunction and cardiovascular disease
In this meta‐analysis, all included studies met the following criteria: (a) case–control studies focused on the association between rs5370/ Lys198Asn polymorphism and ischemic stroke susceptibility, (b) patients with ischemic stroke were diagnosed with neuroimaging confirmed by neurologist, and (c) there were sufficient data of the genotypes in the case–control groups to evaluate the or dominant model (OR) and 95% confidence intervals (CIs)
We found that Lys198Asn single‐nucleotide polymorphism (SNP) was only associated with large vessel infarction but not with lacunar in‐ farction caused by small vessel disease (SVD)
Summary
Stroke is the second leading cause of death globally and leading cause of long‐term disability in both developing and developed countries. K198N or Lys198Asn or rs5370 is a single‐nu‐ cleotide polymorphism (SNP) of EDN1 gene, located in its 5th exon (Tanaka, Kamide, Takiuchi, Miyata, & Kawano, 2005). This SNP leads to G‐to‐T transversion coding for a lysine (K) to asparagine (N) amino acid substitution at amino acid 198 of PPET (Tanaka et al, 2005). This SNP might have a role in altering ET‐1 and leading to vascular dysfunction and ischemic stroke. We conducted a meta‐analysis to investigate the association between Lys198Asn polymorphism of ET‐1 gene (EDN1) and risk of ischemic stroke
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