Mmp-3 And -9 Gene Single Nucleotide Polymorphism And Coronary Heart Disease Susceptibility, As Well As The Degree Of Coronary Atherosclerosis Study

Background:Current evidence suggests that physical disruption of atherosclerotic plaques triggers thrombus formation,which may lead to myocardial infarction(MI).The two major precipitating factors of thrombus formation are disruption of the plaque cap and erosion of its endothelial lining.Inflammation within the atherosclerotic plaque has been suggested to promote the progression toward plaque disruption by causing plaque instability.Inflammatory mediators found in the atheroma have been shown to inhibit smooth muscle growth and collagen production and to augment matrix metalloproteinase(MMP) activity.This can result in decreased collagen content and weakening of plaque structure,leaving the fibrous cap prone to rupture.Matrix metalloproteinases(MMPs),such as stromelysin-1(MMP-3) and gelatinase B(MMP-9),are important in connective tissue remodeling processes associated with atherogenesis and plaque rupture.The functional genetic polymorphisms in the promoters of MMP-3 and MMP-9,which lead to low- and high-transcription activity genotypes,have been shown to be associated with myocardial infarction and angiographically measured atherosclerosis individually,whereas haplotype analysis of the genetic polymorphisms in the promoters and in the coding regions of MMP-3 and MMP-9 is seldom proceeded.Objectives:The aim of the study is to analyze the relation of the -1612 5A/6A,-376C/G,and Glu45Lys polymorphisms of MMP-3 gene and the -1562C/T and R279Q polymorphisms of MMP-9 gene to the risk of coronary heart disease(CHD) in Chinese Han population.Methods:The present study contained 1373 patients with CHD and 695 healthy controls without CHD.The genotyping for these polymorphisms was carried out by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP) analysis.Results:No association of -1612 5A/6A and -376C/G polymorphisms of MMP-3 gene and -1562C/T along with the haplotypes comprising -1562C/T and R279Q polymorphisms of MMP-9 gene with the risk of CHD was found respectively.However, both the Glu45Lys polymorphism of MMP-3 gene and the R279Q polymorphism of MMP-9 gene were associated with the risk of CHD, with an odds ratio of 1.21(p=0.005) and 0.87(p=0.049) for 45Lys(45A) and 279Q(279A) allele individually.Moreover,haplotype analysis identified both the 6A-C-Lys(-1612 6A,-376C,45Lys) haplotype and the 6A-G-Lys(-1612 6A,-376G,45Lys) haplotype were associated with an increased risk of CHD.Conclusion:Our study suggests that common genetic variations in the MMP-3 gene may affect the risk of CHD in Chinese population. Objective Inappropriate extracellular matrix degradation has been implicated to play an important role in atherosclerotic plaque disruption.Matrix metalloproteinases(MMPs) are a family of enzymes which participate in this process.Increased expression of several MMPs and presence of MMP activity has been observed in the chronic inflammation of atherosclerotic arteries.The aim of the present study is to investigate the association between the severity of coronary arteries in the patients with coronary artery disease and the single nucleotide polymorphisms of MMP-3 and MMP-9 genes.Methods One thousand and three hundred seventy-one patients with coronary artery disease diagnosed by coronary angiography were enrolled in this study.The -1612 5A/6A,-376C/G and Glu45Lys polymorphisms of MMP-3 gene and the -1562C/T and R279Q polymorphisms of MMP-9 gene were genotyped by restriction fragment length polymorphism analysis(RFLP) in all subjects. Univariate analysis was applied to measure the association of the single nucleotide polymorphisms with the severity of coronary arteries.Results The 5A allele frequency was significant lower in the group with three vessels stenosis than in the group with single vessel stenosis(OR=0.736,P=0.043).The frequency of the 5A/5A and 5A/6A genotypes was significant lower in the group with three vessels stenosis than in the group with single vessel stenosis(OR=0.740, P=0.041).There was no significant difference in -376G allele frequency(OR=0.984,P=0.874) and the frequency of the genotypes containing the -376G allele(OR=1.035,P=0.801) among the three groups.Similarly,no significant difference in 45Lys allele frequency(OR=0.928,P=0.452) and the frequency of the genotypes containing the 45Lys allele(OR=0.915,P=0.547) were found among the three groups,either.Regarding the polymorphisms of MMP-9 gene,there was no significant difference in -1562T allele frequency(OR=0.866,P=0.359) and the frequency of the genotypes containing the -1562T allele (OR=0.869,P=0.415) among the three groups.Similarly,no significant difference in 279Q allele frequency(OR=0.950,P=0.631) and the frequency of the genotypes containing the 279Q allele(OR=0.864,P=0.294) were found among the three groups,either.Conclusion The -1612 5A/6A polymorphism of MMP-3 gene might be associated with the severity of coronary atherosclerosis assessed by the number of coronary arteries with greater than≥50% stenosis in the Chinese Han patients with coronary heart disease,and the 5A allele might play a protective effect on the progression of coronary atherosclerosis.