Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction

Background-Rupture of the fibrous cap of an atherosclerotic plaque is a key event that predisposes to acute myocardial infarction (AMI). Matrix metall oproteinases (MMPs) may contribute to weakening of the cap, which favors ru pture. Stromelysin, a member of MMP family, is identified extensively in hu man coronary atherosclerotic lesions. It can degrade most of the constituen ts of extracellular matrix as well as activating other MMPs, which suggests that it may play an important role in plaque rupture. Recently, a common v ariant (5A/6A) in the promoter of the stromelysin gene has been identified. The 5A/6A polymorphism could regulate the transcription of the stromelysin gene in an allele-specific manner. Methods and Results-To investigate the relation between the 5A/6A polymorph ism in the promoter of the stromelysin gene and AMI, we conducted a case-co ntrol study of 330 AMI patients and 330 control subjects, The prevalence of the 5A/6A+5A/5A genotype was significantly more frequent in the patients w ith AMI than in control subjects (48.8% vs 32.7%, P<0.0001). In logistic re gression models, the odds ratio of the 5A/6A+5A/5A was 2.25 (95% CI, 1.51 t o 3.35). The association of 5A/6A polymorphism with AMI was statistically s ignificant and independent of other risk factors. Conclusions-The 5A/6A polymorphism in the promoter of the stromelysin gene is a novel pathogenetic risk factor for AMI.