Serum matrix metalloproteinase-3 concentration is influenced by MMP-3 −1612 5A/6A promoter genotype and associated with myocardial infarction

Authors


Dr Ann Samnegård, Cardiology Unit, Division of Medicine, Karolinska Institute Danderyd Hospital, SE-182 88 Stockholm, Sweden.(fax: +46-(0)86226810; e-mail: ann.samnegard@kids.ki.se).

Abstract.

Objectives.  Matrix metalloproteinase-3 (MMP-3) is implicated in the formation of atherosclerotic plaques, and the MMP-3 −1612 5A/6A polymorphism is associated with myocardial infarction (MI) and stable coronary artery disease (CAD). The present study examined whether the −1612 5A/6A polymorphism in the promoter region of the MMP-3 gene influences serum concentrations of MMP-3 and whether serum concentrations of MMP-3 are related to extent of coronary atherosclerosis and risk of MI.

Design and subjects.  This case–control study was conducted in three hospitals in the northern part of Stockholm. A total of 755 MI patients aged below 60 were screened, 433 entered and 387 completed the study. Three hundred and eighty-seven sex- and age-matched control subjects were recruited from the general population of the same county.

Methods.  The MMP-3 genotype was determined by PyrosequencingTM and the serum MMP-3 concentration was quantified with an immunoassay. Severity and extension of CAD was assessed by quantitative coronary angiography in a subgroup of patients (n = 243).

Results.  Patients had lower serum MMP-3 concentration than controls. There was a strong association between MMP-3 −1612 5A/6A genotype and serum concentrations of MMP-3. The presence of one or two copies of the 6A-allele was associated with a graded increase in serum MMP-3. In female patients there was an inverse correlation (r = −0.39, P < 0.05) between serum MMP-3 concentration and plaque area.

Conclusion.  In conclusion, the serum concentration of MMP-3 is influenced by MMP-3 −1612 5A/6A genotype and associated with MI.

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