THE SIGNIFICANCE OF HEMOCHROMATOSIS GENE-MUTATIONS IN THE GENERAL-POPULATION - IMPLICATIONS FOR SCREENING

Background-Haemochromatosis is associated with mutations in the HFE ge ne but the significance of these mutations in the general population i s unknown. Aims-To determine the frequency of HFE gene mutations in th e general population, their effect on serum iron indexes, and their ro le in screening for haemochromatosis. Methods-Deoxyribonucleic acid (D NA) from 1064 randomly selected subjects was analysed for the C282Y an d H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemo chromatosis. Results-Mutations were identified in 409 individuals (38. 4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either muta tion significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C 282Y homozygotes. Five individuals (0.47%) were homozygous for the C28 2Y mutation, three of whom had haemochromatosis confirmed by liver bio psy (0.28%). The other two C282Y homozygotes would not have been detec ted by phenotypic screening alone. Conclusions-HFE mutations are prese nt in 38.4% of the population, affect serum iron indexes, and are impo rtant determinants of iron status. The population frequency of genetic ally defined haemochromatosis (C282Y homozygosity) is approximately on e in 200 and is higher than the prevalence of clinically apparent haem ochromatosis.