Study of the contribution of modulators of iron homeostasis in heart failure

Introduction: Heart failure (HF) is considered one of the biggest public health problems, affecting 2% of the world's population. Is defined as a clinical syndrome due to a structural and/or functional abnormality of the heart that results in elevated intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. It can be influenced by several genetic modulators, in particular genes responsible for the balance of iron (Fe) metabolism, such as the HFE, SLC40A1 and TMPRSS6 genes. Aims: To investigate the contribution of common genetic variants in HFE (C282Y - rs1800562 and H63D - rs1799945), SLC40A1 (rs1439816 and rs2304704) and TMPRSS6 (rs855791) to HF. Material and Methods: The study included a population of 301 HF patients and 361 controls. The polymorphic analysis of the HFE gene variants (C282Y and H63D) was realized using the Multiplex PCR-ARMS technique, while the Endpoint Genotyping PCR technique was used for the remaining variants. Statistical analysis was done using SPSS software, version 28.0, with a statistical significance level of p<0.05. Results: Statistically significant differences were found between patients and controls, in relation to the frequency of the C282Y genotypes. The presence of the Y allele [OR (CI, 95) = 3.127 (1.223-7.995); p = 0.017] was considered a risk factor for HF development. Discussion: Based on the results obtained, the HFE gene was shown to modulate HF. This investigation not only provides a better understanding of the role of HFE in the etiology of HF and is a step forward in personalized medicine, but also underlines the importance of the iron homeostasis in HF. It proposes and reaffirms that the study of iron – related biomarkers as well as HFE common variants should be performed in patients with HF.

Keywords

Heart failure Ferropenic Anemia Genetic Modulation Homeostase do Ferro Doença Cardíaca HFE Polimorfismos Genéticos Metabolismo do Ferro Doenças Genéticas Modificadores Genéticos