HETEROGENEITY OF HEMOCHROMATOSIS IN ITALY

Background & Aims: Patients with hemochromatosis show variable phenoty pe expression. We evaluated the frequency of hemochromatosis gene (HFE ) mutations and the contribution of HFE genotype, ancestral haplotype, ethnic background, and additional factors (alcohol intake, hepatitis viruses, and beta-thalassemia trait) to the severity of iron overload in a large series of Italian patients with a hemochromatosis phenotype . Methods: HFE genotype was studied in 188 patients. Phenotype evaluat ion was available in 153 men and 20 women and was based mainly on iron removed. HFE genotype was determined by a polymerase chain reaction r estriction assay and ancestral haplotype through D6S265 and D6S105 mic rosatellite analysis. Results: The frequency of C282Y homozygotes was 64%, with a decreasing gradient from north to south. C282Y homozygotes showed more severe iron overload than the other HFE genotypes. In the same group, ancestral haplotype was associated with a more severe phe notype. Additional factors may favor the development of a relatively m ild hemochromatosis phenotype in patients nonhomozygous for the C282Y mutation. Conclusions: Hemochromatosis in Italy is a nonhomogenous dis order in which genetic and acquired factors are involved. In patients with a single or no HFE mutation, further studies will enable a differ entiation between true genetic disorders and interactions between gene tic and acquired factors.