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

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.