Association Of MMP-9 Gene Polymorphisms With Myocardial Infarction In A Uighur Population

Objectives: Matrix metalloproteinase-9 (MMP-9) plays a pivotal role in early atherosclerosis, vascular remodeling and development of arterial plaque rupture. The potentially functional MMP-9 polymorphisms may contribute to the susceptibility of myocardial infarction (MI). We aimed to investigate the association between the polymorphisms of three single nucleotide polymorphisms (SNPs) (-1562C>T, R279Q, and R668Q) of the MMP-9 gene and smoking with MI in a Uighur population of China. Methods: A case-control study composed of 384 coronary angiography proven patients with MI and 451 sex-matched and ethnically matched control subjects were enrolled in the study. Among the MI patients,177 had single-vessel disease (46.09%),153 had two-vessel disease (39.85%) and 54 had three-vessel disease (14.06%). The genotypes of the three selected SNPs were determined by the method of Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The relationship between the polymorphisms of the MMP-9 gene and the severity of coronary arterial stenosis was analyzed also. Results:(1) Analysis of three SNPs, the frequency of-1562 CT and TT genotypes in MI group was significantly higher than in control group (25.52% vs.17.29%; P=0.004). And the-1562 T allele showed significant association with MI (MI vs. controls:14.19% vs.9.31%; P=0.002). (2) To R279Q locus, the frequencies of RR,RQ and QQ were 48.18%,39.06% and 12.76% in MI group while ones were 52.99%,37.03% and 9.98% in control group (χ2=2.600, P=0.273). The RQ+QQ genotype and Q-allele frequency in MI group and control group showed not statistically significant differences respectively (all P>0.05). (3) About R668Q polymorphism site, the frequencies of RR,RQ and QQ were 67.71%,27.34% and 4.95% in MI group and 52.99%,37.03% and 9.98% in control group (χ2=2.600, P=0.273). (4) Multiple logistic regression analysis showed that the interaction between-1562T allele and smoking (OR 4.42,95% CI 2.14-7.13; P<0.001) was the independent risk factor of MI, it was high than theindependent effect of smoking (OR=1.89) to MI. (5) The polymorphisms of three SNPs were not statistically different among MI patients with one, two and three or more significantly diseased vessels (all P>0.05). (5) In the haplotypes constructed with-1562C>T, R279Q and R668Q, the T-A-G haplotype was more frequent in the MI group (4%) than in the controls (2.2%) (P=0.029), but the frequency of C-G-A haplotype were lower in the MI patients (5.8%) than in the control group (12.8%) (.P<0.01). (6) Multiple logistic regression analysis showed that diabetes mellitus, hypertension, smoking, total Cholesterol and-1562T allele were independent risk factors of MI. The date also confirmed that T allele carriers (CT or TT genotype) have a higher risk of MI (OR 1.31, 95% CI 1.22-1.40; P=0.004). Conclusions:(1) There findings suggest that MMP-9-1562C>T polymorphism could be associated with the susceptibility to MI in Chinese Uighur population, and the-1562 T allele carriers might be at high risk of the development of MI. (2) Other polymorphisms of R279Q or R668Q were not significantly associated with the risk of MI in this study population. (3) The polymorphisms of three SNPs may not be useful as a predictor of the severity of coronary arterial stenosis. (4) The-1562C>T polymorphism of MMP-9 gene and smoking has a synergistic effect and significantly associated with the risk of MI in Chinese Uighur population. (5) T-A-G haplotype may be associated with the susceptibility to MI and the C-G-A haplotype could be a protective factor respectively of MI in the Uighur population of Xinjiang.