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


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.


CONCLUSIONS
Sequence variants at the MMP-1 genomic locus may influence risk of coronary heart disease in humans.
D000368:Aged; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
D020781:Matrix Metalloproteinase 1