Multiple factors may lead to iron accumulation, causing irreversible organ damage. Homozygosity for the C282Y (C282Y +/+) and compound heterozygosity for the C282Y and H63D (C282Y-H63D) mutations of the HFE gene are associated with susceptibility to iron overload (IO). However, their clinical and biochemical expression is heterogeneous, with some patients showing only an increase of transferrin saturation (TSAT) for life, and others developing severe liver disease at a young age. Rarely, IO occurs in subjects without HFE-mutations or other acquired factors (e.g. alcohol intake, hemolysis, etc.). In these cases, non-HFE hemochromatosis is suspected, but the diagnosis is challenging, based on invasive (i.e., liver biopsy) or poorly available (i.e., Next-Generation Sequencing) approaches. A defective production of the iron regulatory hormone hepcidin is the key pathogenetic factor in hereditary hemochromatosis, irrespective of the gene involved, but extensive studies evaluating its potential diagnostic role are still lacking. This project evaluated hepcidin levels in a large subpopulation from the Cooperative Health Research In South Tyrol (CHRIS) study. Here we explored in particular hepcidin levels in subjects with altered iron status parameters, and their role in the identification of subjects at major risk of developing IO.

Altered iron parameters and hepcidin levels in a general population: lesson from the CHRIS study

busti fabiana
;
castagna annalisa;marchi giacomo;Oliviero Olivieri;girelli Domenico
2019

Abstract

Multiple factors may lead to iron accumulation, causing irreversible organ damage. Homozygosity for the C282Y (C282Y +/+) and compound heterozygosity for the C282Y and H63D (C282Y-H63D) mutations of the HFE gene are associated with susceptibility to iron overload (IO). However, their clinical and biochemical expression is heterogeneous, with some patients showing only an increase of transferrin saturation (TSAT) for life, and others developing severe liver disease at a young age. Rarely, IO occurs in subjects without HFE-mutations or other acquired factors (e.g. alcohol intake, hemolysis, etc.). In these cases, non-HFE hemochromatosis is suspected, but the diagnosis is challenging, based on invasive (i.e., liver biopsy) or poorly available (i.e., Next-Generation Sequencing) approaches. A defective production of the iron regulatory hormone hepcidin is the key pathogenetic factor in hereditary hemochromatosis, irrespective of the gene involved, but extensive studies evaluating its potential diagnostic role are still lacking. This project evaluated hepcidin levels in a large subpopulation from the Cooperative Health Research In South Tyrol (CHRIS) study. Here we explored in particular hepcidin levels in subjects with altered iron status parameters, and their role in the identification of subjects at major risk of developing IO.
Hepcidin, iron overload, ferritin, hemochromatosis, next-generation sequencing
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1011202
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