{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:17:55Z","timestamp":1785403075398,"version":"3.56.0"},"reference-count":25,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novartis"},{"id":[{"id":"https:\/\/ror.org\/0013shd50","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Roche"},{"id":[{"id":"https:\/\/ror.org\/006hrz834","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Instituto Bento da Rocha Cabral"},{"id":[{"id":"https:\/\/ror.org\/030attg11","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Instituto de Sa\u00fade Ambiental"},{"id":[{"id":"https:\/\/ror.org\/03xm57x75","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heart failure (HF) is frequently associated with iron deficiency and anemia, negatively impacting patient outcomes. This study aimed to investigate the contribution of genetic variation in iron metabolism-related genes to biochemical and hematological phenotypes in HF. An HF population of 182 patients with functional iron deficiency (ID) and anemia was stratified by sex and heart failure subtype, including HF with reduced ejection fraction (HFrEF) and HF with non-reduced ejection fraction (HFnrEF). Genetic variants in HFE (rs1799945), SLC40A1 (rs1439816, rs2304704), and TMPRSS6 (rs855791) were evaluated. Variants in HFE and SLC40A1 were associated with differences in serum iron, ferritin, transferrin saturation, hemoglobin, and RDW. The phenotypic impact of these variants was modulated by sex and heart failure subtype, highlighting the influence of iron availability, inflammatory burden, and erythropoietic demand. In contrast, no significant associations were observed for the TMPRSS6 variant. In conclusion, genetic variation in key regulators of iron metabolism contributes to the heterogeneity of iron-related biochemical and hematological phenotypes in HF. These findings emphasize the interplay between genetic background, sex, and heart failure physiology and support the relevance of personalized approaches to iron assessment and management in heart failure.<\/jats:p>","DOI":"10.3390\/ijms27093778","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:08:02Z","timestamp":1777018082000},"page":"3778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Genetics of Iron Metabolism on Biochemical and Hematological Phenotypes of Heart Failure"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4586-4948","authenticated-orcid":false,"given":"M\u00e1rio","family":"Barbosa","sequence":"first","affiliation":[{"name":"Instituto de Sa\u00fade Ambiental, Laborat\u00f3rio Associado TERRA, 1649-028 Lisboa, Portugal"},{"name":"Departamento de Medicina Interna, Hospital Lus\u00edadas, 1500-458 Lisboa, Portugal"},{"name":"Medicine ULisboa for Health, Clinical Research and Innovation, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Instituto de Sa\u00fade Ambiental, Laborat\u00f3rio Associado TERRA, 1649-028 Lisboa, Portugal"},{"name":"Instituto Bento da Rocha Cabral, 1250-047 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Matias","sequence":"additional","affiliation":[{"name":"Medicine ULisboa for Health, Clinical Research and Innovation, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-3274","authenticated-orcid":false,"given":"Joana","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Instituto de Sa\u00fade Ambiental, Laborat\u00f3rio Associado TERRA, 1649-028 Lisboa, Portugal"},{"name":"Medicine ULisboa for Health, Clinical Research and Innovation, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"},{"name":"Instituto Bento da Rocha Cabral, 1250-047 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3353-9470","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Caldeira","sequence":"additional","affiliation":[{"name":"Medicine ULisboa for Health, Clinical Research and Innovation, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5386-6684","authenticated-orcid":false,"given":"Ana","family":"Mel\u00edcio","sequence":"additional","affiliation":[{"name":"Instituto de Sa\u00fade Ambiental, Laborat\u00f3rio Associado TERRA, 1649-028 Lisboa, Portugal"},{"name":"Departamento de Medicina II, Hospital 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