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.

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

“… 13 In a meta-analysis including 1291 cases and 2513 controls, Lys198Asn polymorphism of ET-1 gene was associated with an increased risk of large vessel ischemic stroke. 14 These data show that ET-1 is involved in multiple vascular diseases. Further, administration of endothelin receptor blockers reduces pulmonary vascular resistance and improves symptoms and prognosis in patients with idiopathic PAH.…”

An Overview of Vascular Dysfunction and Determinants: The Case of Children of African Ancestry

“…Three different genes encode endothelin, which gives rise to three different precursors of pre-proendothelin (42). Pre-pro-endothelin-1 is the first product encoded by the ET-1 gene (43). This precursor is transformed into pro-ET-1 by removal of a short sequence by a signal peptidase.…”

A synthesis of pathways linking diet, metabolic risk and cardiovascular disease: a framework to guide further research and approaches to evidence-based practice

“…Recent advances in this area have also highlighted a shared mechanistic pathway involving inflammation and endothelium oxidation in endothelial dysfunction (212,213) . For instance, SNPs involved in processes related to endothelial and vascular health such as vascular endothelial growth factor receptor, platelet/endothelial cell adhesion molecule-, endothelial nitric oxide synthase and endothelin-1 contribute to local and systemic vascular disorders (214)(215)(216)(217)(218) , yet studies had small sample sizes, were limited in number or did not account for gene-environment interaction.…”