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Research Paper|Volume 12, Issue 1|pp 416—435

Association of DIAPH1 gene polymorphisms with ischemic stroke

Zhanyun Ren1, Xiaotian Chen2,3, Wuzhuang Tang1, Jie Li1, Song Yang4, Yanchun Chen4, Xianghai Zhao4, Huihua Zong1, Chunlan Liu3, Chong Shen3
  • 1Department of Neurology, Affiliated Yixing Peopleʼs Hospital of Jiangsu University, Peopleʼs Hospital of Yixing City, Yixing 214200, China
  • 2Department of Clinical Epidemiology, Childrenʼs Hospital of Fudan University, Shanghai 201102, China
  • 3Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China
  • 4Department of Cardiology, Affiliated Yixing Peopleʼs Hospital of Jiangsu University, Peopleʼs Hospital of Yixing City, Yixing 214200, China
* Equal contribution
Received: February 23, 2019Accepted: December 23, 2019Published: January 3, 2020
https://doi.org/10.18632/aging.102631

Copyright: © 2020 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

DIAPH1 is a formin protein involved in actin polymerization with important roles in vascular remodeling and thrombosis. To investigate potential associations of DIAPH1 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. DIAPH1 mRNA expression was compared between 66 IS [43 small artery occlusion (SAO) and 23 large-artery atherosclerosis (LAA)] and 58 controls. Odds ratio (OR), hazard ratio (HR) and 95% confidence interval (CI) were calculated by logistic and cox regression analysis. Rs7703688 T>C variation was significantly associated with an increased risk of IS [OR (95% CI) was 1.721 (1.486-1.993), P=4.139×10-12]. Association of rs7703688 with stroke risk was further validated in the cohort study [adjusted HRs (95% CIs) for additive and recessive models were 1.385 (1.001-1.918), P=0.049, and 2.882 (1.038-8.004), P=0.042, respectively)]. DIAPH1 mRNA expression was significantly downregulated in IS. In SAO stroke subtype, DIAPH1 expression has an increased trend among rs251019 genotypes (Ptrend=0.048). These novel findings suggest that DIAPH1 variation contributes to genetic susceptibility to stroke risk, especially the SAO subtype of IS.