Document Detail


A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis.
MedLine Citation:
PMID:  21173098     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Inadequate hepcidin production leads to iron overload in nearly all types of hemochromatosis. We explored the acute response of hepcidin to iron challenge in 25 patients with HFE-hemochromatosis, in two with TFR2-hemochromatosis and in 13 controls. Sixteen patients (10 C282Y/C282Y homozygotes, 6 C282Y/H63D compound heterozygotes) had increased iron stores, while nine (6 C282Y/C282Y homozygotes, 3 C282Y/H63D compound heterozygotes) were studied after phlebotomy-induced normalization of iron stores.
DESIGN AND METHODS: We analyzed serum iron, transferrin saturation, and serum hepcidin by both enzyme-linked immunosorbent assay and mass-spectrometry at baseline, and 4, 8, 12 and 24 hours after a single 65-mg dose of oral iron.
RESULTS: Serum iron and transferrin saturation significantly increased at 4 hours and returned to baseline values at 8-12 hours in all groups, except in the iron-normalized patients who showed the highest and longest increase of both parameters. The level of hepcidin increased significantly at 4 hours and returned to baseline at 24 hours in controls and in the C282Y/H63D compound heterozygotes at diagnosis. The hepcidin response was smaller in C282Y-homozygotes than in controls, barely detectable in the patients with iron-depleted HFE-hemochromatosis and absent in those with TFR2-hemochromatosis. Conclusions Our results are consistent with a scenario in which TFR2 plays a prominent and HFE a contributory role in the hepcidin response to a dose of oral iron. In iron-normalized patients with HFE hemochromatosis, both the low baseline hepcidin level and the weak response to iron contribute to hyperabsorption of iron.
Authors:
Domenico Girelli; Paola Trombini; Fabiana Busti; Natascia Campostrini; Marco Sandri; Sara Pelucchi; Mark Westerman; Tomas Ganz; Elizabeta Nemeth; Alberto Piperno; Clara Camaschella
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-20
Journal Detail:
Title:  Haematologica     Volume:  96     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-01     Completed Date:  2011-08-16     Revised Date:  2011-11-24    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  500-6     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Verona, Policlinico GB Rossi, 37134 Verona, Italy. domenico.girelli@univr.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Antimicrobial Cationic Peptides / blood*
Ferritins / blood
Genotype
Hemochromatosis / blood*,  genetics*
Histocompatibility Antigens Class I / genetics
Humans
Iron / administration & dosage*,  blood*,  metabolism
Male
Membrane Proteins / genetics
Middle Aged
Receptors, Transferrin / genetics
Time Factors
Grant Support
ID/Acronym/Agency:
GGP06213//Telethon; GGP08089//Telethon
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/HFE protein, human; 0/Histocompatibility Antigens Class I; 0/Membrane Proteins; 0/Receptors, Transferrin; 0/TFR2 protein, human; 0/hepcidin; 7439-89-6/Iron; 9007-73-2/Ferritins
Comments/Corrections
Comment In:
Haematologica. 2011 Apr;96(4):485-8   [PMID:  21454877 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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