Frequency and biochemical expression of C282Y/H63D hemochromatosis (HFE) gene mutations in the healthy adult population in Italy

Background/Aims: The actual prevalence of the main hemochromatosis (HFE) mu tations in the Italian adult population and their phenotypic expression hav e not yet been established. This information is key to advocate a mass-scre ening program. Methods: Two thousand one hundred adults were tested for the C282Y/H63D HFE gene mutations by an automated genotyping assay as well as transferrin sat uration (TS) and serum ferritin levels. Results: No homozygotes for the C282Y mutation were found. Heterozygosity f or the C282Y mutation was 3.1%, while heterozygosity and homozygosity for t he H63D mutation were 21.5% and 2.5%, respectively. TS was significantly hi gher in C282Y heterozygotes and H63D homozygotes as compared to wild-type i ndividuals (P < 0.01). Interestingly, of the HFE wild-type subjects 5.9% ha d a TS value above the 45% threshold. Conclusions: This study shows that (i) the predicted prevalence for C282Y h omozygosity in Italy is 1:3900; (ii) the C282Y/H63D wild-type population ha s an increased baseline of iron parameters possibly due to genetic factors not linked to the C282Y/H63D mutations; (iii) since in the latter populatio n the actual tissue iron burden cannot be assessed, phenotypic (TS) screeni ng in Italy is not recommended until the true prevalence of all mutations i n the HFE gene and in other hemochromatosis genes will be established. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.