Polymorphisms of Matrix Metalloproteinases in Systolic Heart Failure: Role on Disease Susceptibility, Phenotypic Characteristics, and Prognosis

Abstract

Background The role of matrix metalloproteinases (MMPs) polymorphisms on heart failure (HF) susceptibility, phenotypic characteristics, and prognosis has been poorly explored. Methods and Results We studied 313 HF patients with left ventricular systolic dysfunction and 367 healthy control subjects. Genotyping of MMP-1 (−1607 1G/2G), MMP-3 (−1171 5A/6A), and MMP-9 (−1562 C/T) polymorphisms was performed by polymerase chain reaction. Allelic and genotypic frequencies of MMP-1, -3, and -9 were similar in HF patients and controls. MMP1 2G allele carriers were positively associated to ischemic etiology and history of myocardial infarction (all P values <.05). Patients were followed-up for a median of 40 months and 58 HF-related deaths occurred during this period. HF-related survival was significantly better in MMP1 2G allele carriers (71% versus 42% for 1G/1G patients, P = .002) and in MMP-3 6A allele carriers (70% versus 61% for 5A/5A patients, P = .064), particularly in non-ischemic patients ( P = .039). MMP1 2G allele was independently associated to HF survival after adjustment for several other predictors of risk (hazard ratio 0.47, 95% confidence interval 0.27 to 0.82; P = .008). Conclusions MMP-1, -3, and -9 polymorphisms were not associated to HF susceptibility. However, MMP1 2G allele carriers were related to a higher prevalence of ischemic etiology among patients with systolic HF and better HF-related prognosis.