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 C2 82Y 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 H6 3D mutations in patients with mild and marked iron overload and in normal s ubjects. METHODS: A total of 82 patients with iron overload were included in this st udy and had hepatic iron index determination and/or quantitation of iron st ores by phlebotomy. The control group consisted of 81 healthy blood donors. HFE mutation analysis was performed on leukocyte DNA using PCR-amplified g enomic DNA. RESULTS: Of patients with iron overload, 70/82 (85%) were homozygous for C2 82Y 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 mu moles/g dry weight. CONCLUSIONS: In all, 85% of our patients with iron overload were C282Y homo zygotes, 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 ass ociated with iron overload. (Am J Gastroenterol 2000;95: 2910-2914. (C) 200 0 by Am. Coll. of Gastroenterology).