ANALYSIS OF THE CONTRIBUTION OF GENES HP, ACE, HPSE1, MTHFR AND HFE TO THE DEVELOPMENT OF HEART FAILURE

Abstract

Objective: Heart Failure (HF) is a clinical syndrome characterised by typical symptoms, associated with a cardiac incapacity of pumping blood. Although there have been improvements in treating HF, this disease still has a high mortality rate. Genes HP, ACE, HPSE1, MTHFR, and HFE are involved in various events and regulatory mechanisms associated with the disease such as the functionality of Haptoglobin, the activity of ACE and Heparanase enzymes and the metabolisms of Folic Acid and Iron. The purpose of this study is to investigate the contribution of the variants Hp1/2 (HP), I/D (ACE), rs4693608 (HPSE1), C677T (MTHFR), H63D and C282Y (HFE) to the development of HF individually or in epistasis. Design and method: Genotype data previously obtained in 143 HF patients and 246 healthy individuals was used to carry out analysis. The analysis of the data was performed with SPSS software. The association between genotypes and alleles was tested by Chi-Square or Fisher tests. Odds Ratios were calculated as well as the corresponding confidence intervals. Results: We have observed a higher risk for developing HF in the presence of: 1) the T allele [OR (IC, 95) = 2,932] and CT genotype [OR (IC, 95) = 3,618] of the C677T polymorphism; 2) epistasis between II and YY genotypes of the I/D and C282Y polymorphisms [OR (IC, 95) = 5,191]; 3) epistasis between II and DD genotypes of the I/D and H63D polymorphisms [OR (IC, 95) = 6,626]; 4) epistasis between the 2 and C alleles of HP gene and C677T polymorphism [OR (IC, 95) = 4,351]; 5) epistasis between the C and A alleles of the C677T and rs4693608 polymorphisms [OR (IC, 95) = 6,804]. A protective effect was observed for the CC genotype of the C677T polymorphism [OR (IC, 95) = 0,341]; between the D allele of the I/D variation and the Y [OR (IC, 95) = 0,233] and D [OR (IC, 95) = 0,279] alleles of the C282Y and H63D polymorphisms, respectively. Conclusions: We have concluded that HP, ACE, HPSE1, MTHFR, and HFE genes contribute to the susceptibility of developing HF individually or in epistasis.