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Blood, 1 December 2007, Vol. 110, No. 12, pp. 4096-4100. Prepublished online as a Blood First Edition Paper on August 27, 2007; DOI 10.1182/blood-2007-06-096503. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-06-096503v1 110/12/4096    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Piperno, A. Articles by Camaschella, C. Search for Related Content PubMed PubMed Citation Articles by Piperno, A. Articles by Camaschella, C. Related Collections Red Cells Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis Alberto Piperno1, Domenico Girelli2, Elizabeta Nemeth3, Paola Trombini1, Claudia Bozzini2, Erika Poggiali4, Yen Phung3, Tomas Ganz3, and Clara Camaschella4 1 Department of Clinical Medicine and Prevention, Milano-Bicocca University, San Gerardo Hospital, Monza, Italy; 2 Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy; 3 Departments of Medicine and Pathology, David Geffen School of Medicine, University of California, Los Angeles (UCLA); and 4 Vita-Salute San Raffaele University and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy 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 ( 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Kautz, D. Meynard, A. Monnier, V. Darnaud, R. Bouvet, R.-H. Wang, C. Deng, S. Vaulont, J. Mosser, H. Coppin, et al. Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver Blood, August 15, 2008; 112(4): 1503 - 1509. [Abstract] [Full Text] [PDF]

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