Abstract Heart Failure (HF) is frequently associated with iron deficiency and anemia, impacting patient outcomes. This study investigates the contribution of genetic variations in the iron metabolism-related genes HFE (rs1799945), SLC40A1 (rs1439816, rs2304704), and TMPRSS6 (rs855791), to biochemical and hematological phenotypes in HF. We analyzed a population of 127 HF patients, stratifying them into HF with preserved Ejection Frac-tion (HFpEF) and with HF with non-preserved Ejection Fraction (HFnpEF), considering sex-specific differences. The results showed that the HFE rs1799945 variant was signif-icantly associated with increased serum iron and transferrin saturation levels, as well as decreased RDW values. Variants in SLC40A1 were shown to modulate levels of serum iron (rs1439816), ferritin and Hb (rs2304704). In contrast, TMPRSS6 was associated with lower serum iron and transferrin saturation. The outcomes of this study highlighted a particularly relevant contribution from men with HFnpEF. These findings suggest a genetic basis for iron-handling disparities in HF, emphasizing the need for personalized iron management strategies in clinical practice.
Aguiar et al. (Sun,) studied this question.