Functional Polymorphism in the Promoter Region of Matrix Metalloproteinase-9 is Strongly Associated with Acute Myocardial Infarction

Abstract

Background and Objectives:Matrix metalloproteinase-9 (MMP-9) plays an important role in the genesis of atherosclerotic plaque rupture and acute coronary syndrome (ACS), including an acute myocardial infarction (AMI). A single nucleotide polymorphism (SNP) in the MMP-9 promoter (-1562C>T) has recently been identified. This study investigated whether the SNP of the MMP-9 promoter is a significant risk factor for an AMI due to plaque rupture and if SNPs affect the transcription of the gene that elevates the MMP-9 expression level. Subjects and Methods:A polymerase chain reaction, followed by a restriction fragment length polymorphism analysis, was performed in 173 control participants and 206 AMI patients. The serum levels of MMP-9 in the groups with or without the SNP were measured, using ELISA, and compared. Results:There was a significantly higher incidence of the -1562C>T MMP-9 polymorphism in the AMI compared to the control group (27.6% vs. 17.9%, p=0.04). A multiple logistic regression analysis of the risk factors for coronary artery disease and the MMP-9 polymorphism showed the MMP-9 polymorphism to be an important factor in the prediction of an AMI (odds ratio 1.67, 95% confidence interval 1.02-2.67, p=0.04). Conclusion: The -1562C>T polymorphism in the MMP-9 promoter is a definite risk factor for an AMI, and is associated with elevated MMP-9 expression. These results suggest that a SNP in the MMP-9 promoter is strongly associated with an Acute Myocardial Infarction. (Korean Circulation J 2005;35:192-196)