Prevalence and clinical significance of HFE gene mutations in patients with iron overload

OBJECTIVE: The HFE gene contains two mutant alleles; C282Y and H63D. The C282Y mutation occurs in 55-100% of patients with hereditary hemochromatosis. The aim of our study was to re-examine the frequencies of the C282Y and H63D mutations in patients with mild and marked iron overload and in normal subjects. METHODS: A total of 82 patients with iron overload were included in this study and had hepatic iron index determination and/or quantitation of iron stores by phlebotomy. The control group consisted of 81 healthy blood donors. HFE mutation analysis was performed on leukocyte DNA using PCR-amplified genomic DNA. RESULTS: Of patients with iron overload, 70/82 (85%) were homozygous for C282Y versus 2/81 (2.5%) in the control population. Four patients had no HFE mutations despite significant iron overload, including a sister and brother (brother not included in the study group) with hepatic iron concentrations >500 μmoles/g dry weight. CONCLUSIONS: In all, 85% of our patients with iron overload were C282Y homozygotes, although a few had no HFE gene mutations. Pooled data and analysis of chromosomes considered to be at risk for H63D indicate that H63D is associated with iron overload. (C) 2000 by Am. Coll. of Gastroenterology.