Relation between HFE mutations and mild iron-overload expression

The identification of the HFE gene involved in hemochromatosis allows genet ic tests based on mutation analysis to be performed. However, discrepancies in the correlation between HFE genotypes and iron-loading status have aris en. We investigated 708 patients with various signs or symptoms suggesting a putative iron overload that, nevertheless, did not reach the current crit eria for hemochromatosis diagnosis. Most of the patients (91.4%) included i n our study displayed one of three classical iron marker values above the t hreshold defined for iron overloading. HFE mutation analysis allowed us to identify 45.7% of carrier chromosomes in the studied group of patients that showed higher frequencies of HFE mutations compared with controls, In addi tion, the frequencies of compound C282Y/H63D heterozygous, H63D/H63D homozy gous, and C282Y heterozygous genotypes mere higher than those in HH proband s and controls; they accounted for 16, 5.6, and 22.5% of the patients, resp ectively. All genotypic groups had a significantly higher value of serum fe rritin concentration compared to the normal value; only the C282Y homozygot es and compound heterozygotes with H63D had a transferrin saturation signif icantly higher than the normal value. On the whole the H63D homozygous and compound heterozygous patients constitute an intermediate phenotypic group between HH and controls. Some of them may reach the critical overloading de fined for HH diagnosis along with a potential risk of developing complicati ons, whereas others only show a partial phenotypic expression (C) 2000 Acad emic Press.