Polymorphisms of MMP-2 gene are associated with systolic heart failure prognosis

Background: MMP-2 is a proteolytic enzyme involved in myocardial remodeling that occurs in congestive heart failure (HF). We hypothesized MMP-2 genetic variations could influence the prognosis of systolic HF. Methods: To test our hypothesis, we performed a follow-up study of 605 patients with systolic HF. Three single nucleotide polymorphisms (SNPs) of MMP-2 (rs243864, rs243866, rs17859821) were analyzed by restriction fragment length polymorphism (RFLP) methods. Results: Totally 526 patients (86.9%) were followed up. At follow up (median 24 months), 116 patients (22.1%) died, 102 patients (19.4%) were readmitted because of HF. One, two, three and four year survival rate was 86.9%, 81%, 77.9% and 77.9%. MMP-2 rs17859821 A allele carriers had lower all cause death rate, cardiac death rate and MACE rate than did GG genotype carriers (OR=0.655, 0.580, 0.705; P=0.030, 0.008, 0.011). After adjustment for age, bundle branch block, LVEF and NYHA grade by using cox regression analysis, MMP-2 A allele carriers had lower cardiac death rate and MACE rate than did GG genotype carriers(OR = 0.643 and 0.746; P<0.05). However, the genotypes had no association with plasma levels of proMMP-2. Haplotype analysis had confirmed the above results. MMP-2 rs243866, rs243864 had no association with systolic HF prognosis. Conclusion: The findings of the present study suggest that MMP-2 rs17859821 A allele was associated with better prognosis of systolic HF in the northern Han Chinese population. (C) 2009 Published by Elsevier B.V.