Association of DIAPH1 gene polymorphisms with ischemic stroke

Abstract

DIAPH1 is a formin protein involved in actin polymerization with important roles in vascular remodeling and thrombosis. To investigate potential associations of <i>DIAPH1</i> single-nucleotide polymorphisms (SNPs) with hypertension and stroke, 2,012 patients with hypertension and 2,210 controls, 2,966 stroke cases [2,212 ischemic stroke (IS), 754 hemorrhagic stroke (HS)] and 2,590 controls were enrolled respectively in the case-control study. A total of 4,098 individual were included in the cohort study. <i>DIAPH1</i> mRNA expression was compared between 66 IS [43 small artery occlusion (SAO) and 23 large-artery atherosclerosis (LAA)] and 58 controls. Odds ratio (<i>OR</i>), hazard ratio (<i>HR</i>) and 95% confidence interval (<i>CI</i>) were calculated by logistic and cox regression analysis. Rs7703688 T>C variation was significantly associated with an increased risk of IS [<i>OR</i> (95% <i>CI</i>) was 1.721 (1.486-1.993), <i>P</i>=4.139×10^-12]. Association of rs7703688 with stroke risk was further validated in the cohort study [adjusted <i>HRs</i> (95% <i>CI</i>s) for additive and recessive models were 1.385 (1.001-1.918), <i>P</i>=0.049, and 2.882 (1.038-8.004), <i>P</i>=0.042, respectively)]. <i>DIAPH1</i> mRNA expression was significantly downregulated in IS. In SAO stroke subtype, <i>DIAPH1</i> expression has an increased trend among rs251019 genotypes (<i>P_trend</i>=0.048). These novel findings suggest that <i>DIAPH1</i> variation contributes to genetic susceptibility to stroke risk, especially the SAO subtype of IS.