title: Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis.
abstract: Inadequate hepcidin synthesis leads to iron overload in HFE-related hemochromatosis. We explored the regulation of hepcidin by iron in 88 hemochromatosis patients (61 C282Y/C282Y, 27 C282Y/H63D) and 23 healthy controls by analyzing urinary hepcidin before and 24 hours after a 65-mg oral iron dose. Thirty-four patients were studied at diagnosis and had iron overload, and 54 patients were iron depleted. At diagnosis, hepcidin values in C282Y homozygotes were similar to controls, whereas values in C282Y/H63D heterozygotes were higher (P = .02). However, the hepcidin/ferritin ratio was decreased in both homozygotes (P < .001) and heterozygotes (P = .017), confirming the inadequate hepcidin production for the iron load with both genotypes. In iron-depleted patients of both genotypes studied at a time remote from phlebotomy, basal hepcidin was still lower than in controls (P < .001 for C282Y/C282Y and P = .002 for heterozygotes). After an iron challenge, mean urinary hepcidin excretion increased in controls (P = .001) but not patients, irrespective of genotype and iron status. Significant hepcidin increase ( > or = 10 ng/mg creatinine) was observed in 74% of controls, 15% of homozygotes, and 32% of heterozygotes. The hepcidin response to oral iron is blunted in HFE-related hemochromatosis and not improved after iron depletion. The findings support the involvement of HFE in iron sensing and subsequent regulation of hepcidin.
authors.affiliation: Department of Clinical Medicine and Prevention, Milano-Bicocca University, San Gerardo Hospital, Monza, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Piperno
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.forename: Paola
authors.initials: P
authors.lastname: Trombini
authors.forename: Claudia
authors.initials: C
authors.lastname: Bozzini
authors.forename: Erika
authors.initials: E
authors.lastname: Poggiali
authors.forename: Yen
authors.initials: Y
authors.lastname: Phung
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019943:Amino Acid Substitution; D023181:Antimicrobial Cationic Peptides / Q000652:urine*; D003404:Creatinine / Q000652:urine*; D005260:Female; D005293:Ferritins / Q000652:urine*; D006432:Hemochromatosis / Q000235:genetics / Q000652:urine*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D013997:Time Factors
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins; D003404:Creatinine; D007501:Iron