Clinical Significance of TNFRSF1A 36T/C Polymorphism in Cachectic Patients with Chronic Heart Failure

Abstract

Introduction: One of the main factors contributing to the development of nutritional deficits in chronic heart failure (CHF) patients is the systemic inflammatory process. Progressing inflammatory response leads to exacerbation of the disease and could develop into cardiac cachexia (CC), characterized by involuntary weight loss followed by muscle wasting. The aim of this study was to assess the relationship between rs767455 (36 T/C) of the TNFRSF1A and the occurrence of nutritional disorders in CHF patients with cachexia. Materials and Methods: We enrolled 142 CHF individuals who underwent cardiac and nutritional screening in order to assess cardiac performance and nutritional status. The relationship between TNFRSF1A rs767455 genotypes and patients' features was investigated. Results: A greater distribution of the TT genotype among cachectic patients in contrast to non-cachectic individuals was found (TT frequencies of 62.9% and 37.1%, respectively; p = 0.013). We noted a significantly lower albumin concentration (p = 0.039) and higher C-reactive protein (CRP) levels (p = 0.019) in patients with the TT genotype. Regarding cardiac parameters, CHF individuals bearing the TT genotype demonstrated a significant reduction in ejection fraction (EF) (p = 0.033) in contrast to other genotype carriers; moreover, they had a significantly higher concentration of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in the blood (p = 0.018). We also noted a lower frequency of TT genotype carriers among individuals qualified as grades I or II of the New York Heart Association (NYHA) (p = 0.006). The multivariable analysis selected the TT genotype as an unfavorable factor related to a higher chance of cachexia in CHF patients (Odds ratio (OR) = 2.56; p = 0.036). Conclusions: The rs767455TT genotype of TNFRSF1A can be considered as an unfavorable factor related to a higher risk of cachexia in CHF patients.

Keywords: TNFRSF1A; cachexia; cardiac cachexia; chronic heart failure.