Source:http://linkedlifedata.com/resource/pubmed/id/12728308
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2003-5-20
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pubmed:abstractText |
Matrix metalloproteinase-9 (MMP-9) plays an important role in the pathogenesis of atherosclerosis, the pathology underlying the majority of coronary artery disease. We previously identified several polymorphisms in the gene encoding MMP-9. In this study we tested the hypothesis that variation in the matrix metalloproteinase-9 gene influences the development of atherosclerosis. Three common polymorphisms, i.e. -1562C>T, R+279Q and +6C>T, were analysed in 1510 white subjects undergoing coronary angiography. Analyses of individual polymorphisms showed that the frequencies of the C/T and T/T genotypes of the -1562C>T polymorphism were significantly higher in patients with coronary stenosis than in those with a normal angiogram. Logistic regression analyses indicated that individuals carrying the -1562T allele had an approx. 1.5-fold higher risk of developing coronary stenosis (OR 1.49, 95% CI 1.039-2.144), which was equivalent to an over 30% reduction in risk of coronary stenosis in individuals not carrying this allele (OR 0.670, 95% CI 0.467-0.963). The three polymorphisms studied were found to be in strong linkage disequilibrium. Haplotype analyses showed that the C-G-C haplotype (-1562C, +279Q and +6C) was associated with a protective effect against atherosclerosis. Individuals carrying this haplotype were at reduced risk of developing coronary stenosis (OR 0.695, 95% CI 0.530.92). Furthermore, the C-G-C haplotype was associated with less severe coronary atherosclerosis, i.e. carriers of this haplotype were at a lower risk of having coronary stenosis in more than one coronary artery (OR 0.796, 95% CI 0.640.99). These data, together with the previous finding that the -1562T allele has a higher transcriptional activity than the -1562C allele, support the notion that genetic variation with an effect on MMP-9 expression influences the development and progression of atherosclerosis.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0946-2716
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
321-6
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pubmed:dateRevised |
2011-7-8
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pubmed:meshHeading |
pubmed-meshheading:12728308-Case-Control Studies,
pubmed-meshheading:12728308-Coronary Artery Disease,
pubmed-meshheading:12728308-Genetic Predisposition to Disease,
pubmed-meshheading:12728308-Genotype,
pubmed-meshheading:12728308-Haplotypes,
pubmed-meshheading:12728308-Humans,
pubmed-meshheading:12728308-Linkage Disequilibrium,
pubmed-meshheading:12728308-Matrix Metalloproteinase 9,
pubmed-meshheading:12728308-Polymorphism, Single Nucleotide
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pubmed:year |
2003
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pubmed:articleTitle |
Haplotypic analysis of the MMP-9 gene in relation to coronary artery disease.
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pubmed:affiliation |
Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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