Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis

Alberto Piperno, Domenico Girelli, Elizabeta Nemeth, Paola Trombini, Claudia Bozzini, Erika Poggiali, Yen Phung, Tomas Ganz, Clara Camaschella

Research output: Contribution to journalArticle

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, meanurinary hepcidin excretion increased in controls (P = .001) but not patients, irrespective of genotype and iron status. Significant hepcidin increase ( ≥ 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.

Original languageEnglish
Pages (from-to)4096-4100
Number of pages5
JournalBlood
Volume110
Issue number12
DOIs
Publication statusPublished - Dec 1 2007

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Hepcidins
Hemochromatosis
Iron
Heterozygote
Homozygote
Iron Overload
Genotype
Phlebotomy
Ferritins
Creatinine

ASJC Scopus subject areas

  • Hematology

Cite this

Piperno, A., Girelli, D., Nemeth, E., Trombini, P., Bozzini, C., Poggiali, E., ... Camaschella, C. (2007). Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. Blood, 110(12), 4096-4100. https://doi.org/10.1182/blood-2007-06-096503

Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. / Piperno, Alberto; Girelli, Domenico; Nemeth, Elizabeta; Trombini, Paola; Bozzini, Claudia; Poggiali, Erika; Phung, Yen; Ganz, Tomas; Camaschella, Clara.

In: Blood, Vol. 110, No. 12, 01.12.2007, p. 4096-4100.

Research output: Contribution to journalArticle

Piperno, A, Girelli, D, Nemeth, E, Trombini, P, Bozzini, C, Poggiali, E, Phung, Y, Ganz, T & Camaschella, C 2007, 'Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis', Blood, vol. 110, no. 12, pp. 4096-4100. https://doi.org/10.1182/blood-2007-06-096503
Piperno A, Girelli D, Nemeth E, Trombini P, Bozzini C, Poggiali E et al. Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. Blood. 2007 Dec 1;110(12):4096-4100. https://doi.org/10.1182/blood-2007-06-096503
Piperno, Alberto ; Girelli, Domenico ; Nemeth, Elizabeta ; Trombini, Paola ; Bozzini, Claudia ; Poggiali, Erika ; Phung, Yen ; Ganz, Tomas ; Camaschella, Clara. / Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. In: Blood. 2007 ; Vol. 110, No. 12. pp. 4096-4100.
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