Influence of the rs6736 Polymorphism on Ischemic Stroke Susceptibility in Han Chinese Individuals via the Disruption of miR-7-1 Binding to the C14orf119 Gene.

Abstract

This study investigates the association between the C14orf119 gene rs6736 polymorphism and ischemic stroke (IS) susceptibility, and explores the influence of the rs6736 polymorphism on the binding between miR-7-1 and the C14orf119 gene. mRNA expression levels were determined in 45 IS patients and 45 matched controls via real-time quantitative PCR. A total of 774 IS patients and 793 matched controls were recruited from a Han Chinese population for genotyping, performed with the Sequenom MassARRAY iPLEX platform. A dual-luciferase reporter assay was used for the analysis of miRNA-mRNA binding. The results showed that the mRNA expression of C14orf119 differed significantly between IS patients and controls (t = -2.235, P = 0.030). Significant associations were noted between the C14orf119 gene rs6736 polymorphism and IS susceptibility in Han Chinese individuals under the additive model [ORadj (95% CI) = 0.87 (0.76-1.00) Padj = 0.048] and dominant model [ORadj (95% CI) = 0.76 (0.61-0.94), Padj = 0.014], with adjustment for age and sex. Mutations in the rs6736 polymorphism disrupted the binding of miR-7-1 and the C14orf119 gene. The results of this study show that the rs6736 polymorphism in the 3'-untranslated region of the C14orf119 gene not only is associated with IS but also modifies the binding between miR-7-1 and the C14orf119 gene. The C14orf119 gene may participate in the relationship between IS and miR-7-1.