Assessment of the role of matrix metalloproteinase-3 gene polymorphism in the development of chronic heart failure

Abstract

To study the impact of a polymorphic variant of the matrix metalloproteinase-3 (MMP-3) gene on the development and course of chronic heart failure (CHF) in patients with coronary heart disease. A total of 277 patients with New York Heart Association (NYHA) Functional Class (FC) II-IV CHF were examined. MMP-3 -1171 5A/6A genetic polymorphism was studied by polymerase chain reaction. A control group included 136 patients (mean age 53.6 ± 4.8 years) with no signs of cardiovascular diseases, as evidenced by the examination. The frequency of the 5A allele and the 5A/5A genotype of the 1171 5A/6A polymorphic locus in the MMP-3 gene proved to be higher in the patients with CHF than that in the control group. Thus, the variability of the 5A allele (odds ratio (OR), 1.39; 95% confidence interval (CI): 1.033 to 1.869; p = 0.03) and the 5A/5A genotype (OR, 2.15; 95% CI: 1.131 to 4.070; p = 0.02) was associated with increased risk for CHF. There were significant differences in the frequency of MMP-3 alleles and genotypes in relation to FC of CHF. The frequency of the 5A/5A genotype was substantially higher in the patients with NYHA FC IV CHF than that in those with NYHA FC II CHF (32.8% versus 15.2%; p = 0.039). The frequency of the 5A allele was significantly higher in the patients with NYHA FC IV CHF than that in those with NYHA FC II CHF (55.5% and 39.3%; respectively; p = 0.019). Thus, the carriage of the 5A allele and the 5A/5A genotype of the 1171 5A/6A polymorphic locus in the MMP-3 gene is a risk factor of severe CHF. The determination of MMP-3 -1171 5A/6A polymorphism may be recommended for the early prediction of a risk for the development and severe course of CHF.