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Research Paper|Volume 11, Issue 16|pp 6569—6583

Genetic variants of ADAMTS7 confer risk for ischaemic stroke in the Chinese population

Linfa Chen1,2, Weidong Hu1,2, Shengnan Li1,3, Shaoyu Yao4, Mengxu Wang1,2, Xinglan Chen1,2, Shaofeng Chen1,2, Fu Deng1,2, Peiyi Zhu1,2, Keshen Li1,3, Wangtao Zhong2, Bin Zhao1,3, Guoda Ma1,3, You Li1,3
  • 1Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
  • 2Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
  • 3Institute of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China
  • 4Department of Nursing, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
* Equal contribution
Received: February 27, 2019Accepted: August 13, 2019Published: August 28, 2019
https://doi.org/10.18632/aging.102211

Copyright © 2019 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Large-scale genome-wide association analyses show an association between ADAMTS7 variations and coronary risk. However, the link between ADAMTS7 variability and ischaemic stroke (IS) has yet to be determined. This study evaluated ADAMTS7 variants with respect to the risk of IS. Genetic association analyses were performed in two independent case-control cohorts with 1279 patients with IS and 1268 age-matched healthy controls. Four variant genotypes of the ADAMTS7 gene were identified using the Multiplex SNaPshot assay. The rs3825807, rs11634042, and rs7173743 variants of ADAMTS7 were related to lower IS risk in both initial and replication cohort. The G-T-T-C and G-T-C-C haplotypes are significantly less prevalent in the IS group than in the control group. Further stratification according to IS subtypes indicated that carriers with the variant alleles of the rs3825807, rs11634042 and rs7173743 variants of ADAMTS7conferred a lower risk of developing large-artery atherosclerosis stroke subtype. Also, the mutated rs3825807 G allele, as well as the mutated rs11634042 T allele of ADAMTS7, are linked to a significant reduction of ADAMTS7 in patients with IS. Our findings confirm the role of ADAMTS7 in the pathophysiology of IS, with potentially significant implications for the prevention, treatment, and development of novel therapies for IS.