Copyright © 2004 by the European Society of Cardiology.
Clinical research
Prognostic impact of matrix metalloproteinase gene polymorphisms in patients with heart failure according to the aetiology of left ventricular systolic dysfunction
a INSERM U508, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille cedex, France
b Hôpital Cardiologique, Service de Cardiologie C, Centre Hospitalier Universitaire de Lille, Place de Verdun, 59037 Lille cedex, France
Received April 10, 2003;
revised January 14, 2004;
accepted January 22, 2004
* Corresponding author. Tel.: +33-3-20-44-50-45; fax: +33-3-20-44-48-81
E-mail address: cbauters{at}chru-lille.fr
See page 631 for the editorial comment on this article1
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 5A6A MMP-3, and –1562 CT 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 
). The MMP-3 5A/5A genotype was an independent predictor of cardiac mortality (HR 2.92 [1.23–6.69]; 
) 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 
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]; 
). 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.
Key Words: Heart failure • Polymorphism • Genetic • Survival • Matrix • Remodelling
List of Abbreviations: ACE: angiotensin-converting enzyme • ECM: extracellular matrix • HF: heart failure • LV: left ventricular • LVEDD: left ventricular end-diastolic diameter • LVEF: left ventricular ejection fraction • MMP: matrix metalloproteinase • NYHA: New York Heart Association • VO2: oxygen consumption
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