[Pathophysiology and genetics of classic HFE (type 1) hemochromatosis].
Hereditary type 1 HFE hemochromatosis is associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene (C282Y mutation). The p.Cys282Tyr mutation of the HFE gene leads to an abnormal reduction in hepatic expression of hepcidin, a protein that appears to control the release of iron from enterocytes and macrophages towards plasma. Abnormally low hepcidin levels promote an increase in the bioavailability of plasma iron, characterized by elevated transferrin saturation and the appearance of non transferrin bound iron. This nontransferrin-bound iron is avidly taken up by the liver, heart, and pancreas, the principal target organs for systemic iron overload. The variable penetrance of this disease is related to environmental and genetic factors. Among the genetic factors, mutations of some newly identified genes may aggravate the phenotype of iron overload associated with homozygosity for the p.Cys282Tyr mutation of the HFE gene; these new genes include those of hemojuvelin (HJV), transferrin receptor 2 (TfR2), and hepcidin (HAMP).
Loréal
Olivier
O
Inserm U-522, IFR140, Université de Rennes 1. olivier.loreal@rennes.inserm.fr
Ropert
Martine
M
Mosser
Annick
A
Déhais
Valérie
V
Deugnier
Yves
Y
David
Véronique
V
Brissot
Pierre
P
Jouanolle
Anne-Marie
AM
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood; D015227:Lipid Peroxidation; D008565:Membrane Proteins / Q000235:genetics*; D018384:Oxidative Stress / Q000502:physiology; D017354:Point Mutation / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics
D023181:Antimicrobial Cationic Peptides; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C103673:HFE protein, human; C481006:HJV protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D007501:Iron