title: Association of hepcidin promoter c.-582 A>G variant and iron overload in thalassemia major.
abstract: Hepcidin is a 25-amino acid peptide, derived from cleavage of an 84 amino acid pro-peptide produced predominantly by hepatocytes. This molecule, encoded by the hepcidin antimicrobial peptide (HAMP) gene shows structural and functional properties consistent with a role in innate immunity. Moreover, as demonstrated in mice and humans, hepcidin is a major regulator of iron metabolism, and acts by binding to ferroportin and controlling its concentration and trafficking. In this study we investigated the influence that mutations in HAMP and/or hemocromatosis (HFE) genes might exert on iron metabolism in a group of poly-transfused thalassemic patients in preparation for bone marrow transplantation. Our results showed that the presence of the c.-582 A>G polymorphism (rs10421768) placed in HAMP promoter (HAMP-P) might play a role in iron metabolism, perhaps varying the transcriptional activation that occurs through E-boxes located within the promoter.
authors.affiliation: Laboratorio di Immunogenetica e Biologia dei Trapianti, Fondazione IME, Policlinico Tor Vergata, Viale Oxford 81, Rome, Italy. m.andreani@fondazioneime.org
authors.forename: Marco
authors.initials: M
authors.lastname: Andreani
authors.forename: Francesca Clementina
authors.initials: FC
authors.lastname: Radio
authors.forename: Manuela
authors.initials: M
authors.lastname: Testi
authors.forename: Carmelilia
authors.initials: C
authors.lastname: De Bernardo
authors.forename: Maria
authors.initials: M
authors.lastname: Troiano
authors.forename: Silvia
authors.initials: S
authors.lastname: Majore
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Bertucci
authors.forename: Paola
authors.initials: P
authors.lastname: Polchi
authors.forename: Renata
authors.initials: R
authors.lastname: Rosati
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics* / Q000378:metabolism; D001803:Blood Transfusion; D002648:Child; D005260:Female; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D008297:Male; D051379:Mice; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism / Q000628:therapy
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D007501:Iron