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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2005-11-14
pubmed:abstractText
Myocardial infarction (MI) is commonly caused by atherosclerotic plaque rupture following excessive degradation of collagen fibers in the atherosclerotic lesion. We investigated whether interindividual variability in risk of MI was related to polymorphisms in the gene encoding matrix metalloproteinase (MMP)-1, a key fibrillar collagen-degrading enzyme. Several single nucleotide polymorphisms in the MMP1 gene promoter were identified following sequencing DNA samples from 30 individuals. An analysis of the polymorphisms in a cohort of British whites with coronary atherosclerosis, including 639 patients with MI and 538 non-MI subjects, revealed a haplotype effect of the -519A>G and -340T>C polymorphisms on risk of MI, with the A(-519)-C(-340) and G(-519)-T(-340) haplotypes being protective (odds ratio=0.70 [0.57 to 0.86]; P=0.0007), whereas the G(-519)-C(-340) haplotype increased MI risk (odds ratio=1.94 [1.15 to 3.28]; P=0.013). This finding was replicated in a subsequent analysis of 387 Swedish MI patients and 387 healthy controls (odds ratio=0.70 [0.55 to 0.89], P=0.003, for A(-519)-C(-340) and G(-519)-T(-340); odds ratio=1.54 [0.97 to 2.46], P=0.07, for G(-519)-C(-340)). In vitro assays showed that compared with the A(-519)-T(-340) haplotype, the A(-519)-C(-340) and G(-519)-T(-340) haplotypes had lower promoter activity, whereas the G(-519)-C(-340) haplotype had greater promoter strength, in driving gene expression in human macrophages. Haplotype-specific differences in MMP1 mRNA level in atherosclerotic tissues were also detected. The data indicate that MMP1 gene variation is a genetic factor contributing to interindividual differences in MI risk.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1070-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Haplotype effect of the matrix metalloproteinase-1 gene on risk of myocardial infarction.
pubmed:affiliation
Human Genetics Division, School of Medicine, University of Southampton, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't