Document Detail

Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease.
MedLine Citation:
PMID:  12103254     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Our hypothesis was that functional polymorphisms in matrix metalloproteinase (MMP) genes may act as susceptibility factors for the development of coronary aneurysms (CAs). BACKGROUND: Different forms of remodeling have been described at the level of coronary arteries; CA, reported in 1% to 5% of patients with angiographic evidence of coronary artery disease (CAD), are one of them. Matrix metalloproteinases have been implicated in the pathogenesis of aneurysm development through increased proteolysis of extracellular matrix proteins. METHODS: We screened 3,862 patients who underwent coronary angiography and identified 113 patients with CAD with at least one CA (CA group); these patients were matched with 226 patients with CAD without CA (control group). The -1,306 C/T MMP-2, 5A/6A MMP-3, CA-repeat MMP-9 and -82 A/G MMP-12 polymorphisms were determined. RESULTS: The MMP-2, MMP-9 and MMP-12 polymorphisms were not associated with CA. By contrast, the 5A/5A genotype of MMP-3 was significantly more frequent in the CA group than in the control group (31% vs. 18%, p = 0.015); similarly, the MMP-3 5A allele was more frequent in the CA group (p = 0.009). Three variables were independently associated with CA: the MMP-3 5A/5A genotype (odds ratio [OR] = 2.23, 95% confidence interval [CI] [1.27 to 3.93]), a previous myocardial infarction (OR = 1.91, 95% CI [1.14 to 3.20]) and a history of aortic aneurysm (OR = 21.06, 95% CI [2.35 to 188]). CONCLUSIONS: The MMP-3 5A allele is associated with the occurrence of CA. Our results suggest that an increased proteolysis in the arterial wall may act as a susceptibility factor for the development of CA in patients with coronary atherosclerosis.
Nicolas Lamblin; Christophe Bauters; Xavier Hermant; Jean-Marc Lablanche; Nicole Helbecque; Philippe Amouyel
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  40     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-09     Completed Date:  2002-07-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  43-8     Citation Subset:  AIM; IM    
Centre Hospitalier Universitaire de Lille, Lille Cedex, France.
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MeSH Terms
Case-Control Studies
Coronary Aneurysm / genetics*
Coronary Artery Disease / genetics
Gene Frequency
Matrix Metalloproteinase 12
Matrix Metalloproteinase 2 / genetics*
Matrix Metalloproteinase 3 / genetics*
Matrix Metalloproteinase 9 / genetics*
Metalloendopeptidases / genetics*
Middle Aged
Multivariate Analysis
Polymorphism, Genetic*
Promoter Regions, Genetic / genetics*
Reg. No./Substance:
EC 3.4.24.-/Metalloendopeptidases; EC Metalloproteinase 3; EC Metalloproteinase 2; EC Metalloproteinase 9; EC protein, human; EC Metalloproteinase 12

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