Positive Association between EDN1 rs5370 (Lys198Asn) Polymorphism and Large Artery Stroke in a Ukrainian Population

Abstract

There are a lot of convincing evidences about the involvement of endothelin pathway proteins in the pathogenesis of atherosclerosis and its fatal complications. In this study, the analysis of a possible association between EDN1 rs5370 and EDNRA rs5335 gene polymorphisms and the risk of large artery stroke (LAS) in a Ukrainian population was conducted. 200 LAS patients and 200 unrelated controls were enrolled in a case-control study. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was used for SNP genotyping. Our results revealed that EDN1 rs5370 polymorphism was associated with LAS development both before and after adjustment for atherosclerosis risk factors (sex, age, body mass index, arterial hypertension, type 2 diabetes mellitus, and smoking). The risk for a LAS incident in rs5370-T allele carriers was 1.6 times higher (CI = 1.066–2.403; P = 0.020) than in subjects with the GG genotype. No link between EDNRA rs5335 and LAS risk in a Ukrainian population was found. The present study indicated that EDN1 rs5370, but not EDNRA rs5335, can be the strong genetic predictor for LAS development in a Ukrainian population.

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

“…Such SNP may not have influence on disease susceptibility however they can be an important maker if they coinherit with other highly disease-associated gene or with other highly functional SNP of same gene. Dubovyk et al (2018) and Zhang and Sui (2014) provided inconsistent results due to low statistical power. This may be due to a number of issues, including sample size, heterogeneous pathophysiology, and silent SVD.…”

“…Some studies have found that Lys198Asn is associated with ischemic stroke (Dubovyk, Oleshko, Harbuzova, & Ataman, 2018;Li Wei et al, 2009;Yamaguchi et al, 2006;Zhang & Sui, 2014). Some studies have found that Lys198Asn is associated with ischemic stroke (Dubovyk, Oleshko, Harbuzova, & Ataman, 2018;Li Wei et al, 2009;Yamaguchi et al, 2006;Zhang & Sui, 2014).…”

“…Two studies were from China (Li Wei et al, 2009;Zhang & Sui, 2014) and one study was from Japan (Yamaguchi et al, 2006), the United Kingdom (Gormley et al, 2005), Turkey (Aslan et al, 2017), and Ukraine (Dubovyk et al, 2018) each. Two studies were from China (Li Wei et al, 2009;Zhang & Sui, 2014) and one study was from Japan (Yamaguchi et al, 2006), the United Kingdom (Gormley et al, 2005), Turkey (Aslan et al, 2017), and Ukraine (Dubovyk et al, 2018) each.…”

“…This SNP might have a role in altering ET-1 and ultimately leading to vascular dysfunction and ischemic stroke. Some studies have found that Lys198Asn is associated with ischemic stroke (Dubovyk, Oleshko, Harbuzova, & Ataman, 2018;Li Wei et al, 2009;Yamaguchi et al, 2006;Zhang & Sui, 2014). However, few studies have failed to demonstrate this relationship in ischemic stroke (Aslan, Gurger, Atescelik, & Kara, 2017;Gormley, Bevan, Hassan, & Markus, 2005).…”

“…Additionally, these studies are limited by their small sample size (Aslan et al, 2017;Dubovyk et al, 2018;Gormley et al, 2005;Li Wei et al, 2009;Yamaguchi et al, 2006;Zhang & Sui, 2014). Thus, we conducted a meta-analysis to investigate the association between Lys198Asn polymorphism of ET-1 gene (EDN1) and risk of ischemic stroke.…”