Association of hepcidin promoter c.-582 A>G variant and iron overload in thalassemia major.
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.
Andreani
Marco
M
Laboratorio di Immunogenetica e Biologia dei Trapianti, Fondazione IME, Policlinico Tor Vergata, Viale Oxford 81, Rome, Italy. m.andreani@fondazioneime.org
Radio
Francesca Clementina
FC
Testi
Manuela
M
De Bernardo
Carmelilia
C
Troiano
Maria
M
Majore
Silvia
S
Bertucci
Pierfrancesco
P
Polchi
Paola
P
Rosati
Renata
R
Grammatico
Paola
P
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
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D007501:Iron