Variation in the matrix metalloproteinase-1 gene and risk of coronary heart disease

Ye, Shu, Gale, Catharine R. and Martyn, Christopher N. (2003) Variation in the matrix metalloproteinase-1 gene and risk of coronary heart disease. European Heart Journal, 24 (18), 1668-1671. (doi:10.1016/S0195-668X(03)00385-3).

Abstract

Aims: Matrix metalloproteinase-1 (MMP-1), a proteolytic enzyme able to degrade types I and III collagens, is present in atherosclerotic lesions but absent from the normal blood vessel wall. The recent observation that, in a transgenic mouse model, MMP-1 gene expression slows the development and progression of atherosclerotic plaques suggests that it may play a role in human atherogenesis. We investigated whether coronary heart disease was associated with a functional polymorphism in the human MMP-1 gene. In addition, we examined a polymorphism in the human MMP-3 gene that was previously reported to be associated with progression of coronary atherosclerosis.

Methods and Results: We genotyped 471 Caucasian men and women, aged 66-75 years, from Sheffield, UK, for the 1G/2G polymorphism in the MMP-1 gene and the 5A/6A polymorphism in the MMP-3 gene and ascertained the prevalence of coronary heart disease. People homozygous for the more transcriptionally active 2G allele of the MMP-1 gene had a reduced risk of coronary heart disease (OR 0.5, 95% CI 0.3 to 0.9) compared to people homozygous for the less transcriptionally active 1G allele. Heterozygotes had an intermediate risk (OR 0.7, 95% CI, 0.5 to 1.1). We found no association between the 5A/6A polymorphism in the MMP-3 gene and risk of coronary heart disease.

Conclusion: Sequence variants at the MMP-1 genomic locus may influence risk of coronary heart disease in humans.

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Contributors

Author: Catharine R. Gale

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