Copyright © 2003 by the European Society of Cardiology.
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Variation in the matrix metalloproteinase-1 gene and risk of coronary heart disease
a Human Genetics Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK
b MRC Environmental Epidemiology Unit (University of Southampton), Southampton General Hospital, Southampton SO16 6YD, UK
* Corresponding author. Dr C. R. Gale, University of Southampton, MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton, Hants SO16 6YD, UK. Tel.: +44-23-80764080; fax: +44-23-80704021. Address for reprints: Dr S Ye, Human Genetics Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK.
E-mail address: crg{at}mrc.soton.ac.uk
Received 15 October 2002; revised 12 June 2003; accepted 2 July 2003
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.
Key Words: Coronary heart disease • Matrix metalloproteinase-1 • Matrix metalloproteinase-3 • Gene expression • Polymorphism • Epidemiology
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