Relationship of polymorphisms in the tissue inhibitor of metalloproteinase (TIMP)-1 and -2 genes with chronic heart failure

Abstract

Dysregulated expression of tissue inhibitors of matrix metalloproteinases (TIMPs) is associated with systolic dysfunction and worsening heart failure (HF). However, no study has assessed the relationship between TIMP polymorphisms and chronic HF. In this study, 300 HF outpatients with reduced left ventricular ejection fraction and 304 healthy blood donors were genotyped for the 372 T > C polymorphism (Phe124Phe; rs4898) in the TIMP-1 gene and the −418 G > C polymorphism (rs8179090) in the TIMP-2 gene to investigate whether these polymorphisms are associated with HF susceptibility and prognosis. The genotype and allele frequencies of the 372 T > C polymorphism in HF patients were not significantly different from those observed among healthy subjects, and the C allele of the −418 G > C polymorphism was very rare in our population (frequency < 1%). After a median follow-up duration of 5.5 years, 121 patients (40.3%) died (67 of them from HF). Survival analysis did not show statistically significant differences in all-cause death and HF-related death between patients with and without the T allele (P > 0.05 for all comparisons). Thus, our findings do not support the hypothesis that the 372 T > C (Phe124Phe) polymorphism in the TIMP-1 gene and the −418 G > C polymorphism in the TIMP-2 gene are associated with HF susceptibility and prognosis in Southern Brazilians.