Variations in matrix metalloproteinase-1, -3, and -9 genes and the risk of acute coronary syndrome and coronary artery disease in the Chinese Han population

Abstract

Matrix metalloproteinases (MMPs) are a group of endopeptidases involved in the pathogenesis of atherosclerosis, and MMP gene polymorphisms may contribute toward the risk of coronary heart disease. Within this context, our aim was to examine whether MMP1, MMP3, and MMP9 gene polymorphisms are associated with susceptibility to acute coronary syndrome (ACS) or angiographic coronary artery disease (CAD). The MMP1 -519 A/G, MMP3 -1171 5A/6A, and MMP9 -1562 C/T polymorphisms were evaluated in 1574 individuals. Genotypes of patients with ACS (n=660) and angiographically defined CAD (n=382) were compared with ACS-free (n=914) and non-CAD controls (n=466). The MMP3 5A allele occurred at a higher frequency in patients with ACS than in ACS-free individuals (P=0.001). Logistic regression analysis showed that the 5A/5A genotype of MMP3 was associated with a significantly increased risk of ACS [adjusted odds ratio (OR)=2.297, 95% confidence interval (CI)=1.105-4.775, P=0.026, 5A/5A vs. 6A/6A]. The CT and TT variant genotypes of MMP9 were associated with the occurrence of CAD (adjusted OR=1.425, 95% CI=1.045-1.943, P=0.025, CT+TT vs. CC). None of the MMP1 -519 A/G polymorphisms was associated with ACS or CAD. Because of linkage disequilibrium, MMP1 and MMP3 polymorphisms were combined on chromosome 11q22.3, and the 5A-1171-G-519 haplotype had a genetic risk factor for ACS (OR=1.505, 95% CI=1.219-1.857, P=0.00013), whereas the 6A-1171-G-519 haplotype had a decreased risk of ACS (OR=0.815, 95% CI=0.677-0.981, P=0.03). Taken together, the present findings indicate that genetic variations in MMP3 and MMP9 genes may be useful genetic markers for determining susceptibility to CAD in the Chinese Han population.