Association of SNPs in the TIMP-2 gene and large artery atherosclerotic stroke in southern Chinese Han population.

Tie Guo,Lv Zhou,Feng Zhou,Dan Yu,Haizhen Hao

doi:10.18632/oncotarget.23473

Abstract

Tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) regulates the extracellular matrix degradation, which involved in vascular remodeling and dysfunction, destabilization of atherosclerotic plaque and many other pathological processes. The rupture of atherosclerotic plaque is the trigger of Large artery atherosclerotic (LAA) stroke. We speculate that the Single nucleotide polymorphisms (SNPs) in TIMP-2 may have an association with LAA stroke. To prove this hypothesis, we conducted this case-control study. 250 LAA stroke patients and 250 healthy controls were collected for the analysis of TIMP-2 polymorphisms. Among six SNPs, we detected no deviation from Hardy-Weinberg equilibrium in control group. There was a significant difference in rs4789936 T allele frequency between patient and control groups (OR = 0.68, 95% CI = 0.51–0.91, P = 0.009), which means lower risk of LAA stroke. We observed the rs4789936 had a decreased risk of LAA stroke according to the codominant (OR = 0.64, 95% CI = 0.44–0.92, P = 0.026), dominant (OR = 0.62, 95% CI = 0.43-0.88, P = 0.008), overdominant (OR = 0.68, 95% CI = 0.48–0.98, P = 0.039), log-additive (OR = 0.68, 95% CI = 0.51–0.91, P = 0.009) models analyses. However, these findings could only validate under dominant model (OR = 0.65, 95% CI = 0.42–1.00, P = 0.049) after adjustment of gender and age. The results indicate a potential association between TIMP-2 variants and LAA stroke risk in southern Chinese Han population.

Highlights

Ischemic stroke, one of the most complex vascular disease with highly morbidity and mortality, continues to be a major global health problem among worldwide [1]
We speculate that the Single nucleotide polymorphisms (SNPs) in Tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) may have an association with Large artery atherosclerotic (LAA) stroke
It is obvious that information obtained from the table with regard to the SNPs and their chromosomal position, allele, minor allele frequency for cases and controls, and Hardy-Weinberg equilibrium (HWE) test results

Summary

Introduction

One of the most complex vascular disease with highly morbidity and mortality, continues to be a major global health problem among worldwide [1]. Conventional risk factors like hypertension, dyslipidemia, drinking and smoking are relation to the etiology of ischemic stroke [2]. LAA stroke has the highest risk of early neurological deterioration and early stroke recurrence than other acute ischemic stroke (AIS) subtypes [6]. The process of LAA stroke is usually begin with the vulnerable plaque rupture, accompanying by the formation of thrombus and occlusion of a cerebral artery, and leading to irreversible brain damage, blood brain barrier (BBB) disruption, and cellular edema [7]. The rupture of vulnerable atherosclerotic plaques is an important cause of cerebral infarction [8]. Whether cerebral infarction occurs in atherosclerotic patients, is related to the levels of MMPs and TIMPs in blood [11]

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Methods

Results