Document Detail

Prognostic impact of matrix metalloproteinase gene polymorphisms in patients with heart failure according to the aetiology of left ventricular systolic dysfunction.
MedLine Citation:
PMID:  15084374     Owner:  NLM     Status:  MEDLINE    
AIMS: To assess the possible effect of functional polymorphisms in matrix metalloproteinase (MMP) gene promoters on the clinical outcome of patients with heart failure. METHODS AND RESULTS: We studied 444 consecutive patients who were referred to our centre for evaluation of left ventricular dysfunction. We extracted genomic DNA from white blood cells and determined the -1306 C >T MMP-2, -1171 5A > 6A MMP-3, and -1562 C >T MMP-9 polymorphisms. Clinical follow-up (median 717 days) was obtained for 443 patients. The MMP-3 polymorphism had a different impact on cardiac survival in HF patients with ischaemic and non-ischaemic cardiomyopathy (interaction p <0.03). The MMP-3 5A/5A genotype was an independent predictor of cardiac mortality (HR 2.92 [1.23-6.69]; p = 0.01) in patients with non-ischaemic HF. In contrast, there was no evidence for any effect of the MMP-3 genotype on cardiac events in patients with ischaemic cardiomyopathy. The MMP-9 polymorphism was associated with cardiac survival (p < 0.03) independently of HF aetiology. In multivariate analysis, the MMP-9 T allele was an independent predictor of cardiac mortality (HR 1.81 [1.09-3.02]; p = 0.02). Finally, there was no evidence for any association between MMP-2 polymorphism and cardiac survival. CONCLUSION: MMP-3 and MMP-9 polymorphisms contribute to variability in cardiac survival in HF patients. These data suggest that MMP genotyping could provide important additional information for refining risk stratification in patients with heart failure. MMP genotyping may help to select patients who could benefit from MMP inhibition.
Frédérique Mizon-Gérard; Pascal de Groote; Nicolas Lamblin; Xavier Hermant; Jean Dallongeville; Philippe Amouyel; Christophe Bauters; Nicole Helbecque
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European heart journal     Volume:  25     ISSN:  0195-668X     ISO Abbreviation:  Eur. Heart J.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-04-15     Completed Date:  2004-08-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  England    
Other Details:
Languages:  eng     Pagination:  688-93     Citation Subset:  IM    
INSERM U508, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille cedex, France.
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MeSH Terms
Exercise Test
Heart Failure / genetics*,  mortality
Matrix Metalloproteinases / genetics*
Middle Aged
Polymorphism, Genetic / genetics*
Survival Analysis
Ventricular Dysfunction, Left / genetics*,  mortality
Ventricular Remodeling / genetics
Reg. No./Substance:
EC 3.4.24.-/Matrix Metalloproteinases
Comment In:
Eur Heart J. 2004 Apr;25(8):631-3   [PMID:  15084366 ]

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