Haemochromatosis-associated HFE genotypes in English blood donors: age-related frequency and biochemical expression

Background/Aims: There are limited data on the frequency and biochemical expression of the haemochromatosis-associated mutations C282Y and H63D in healthy people. Methods: We genotyped (bi-directional PCR amplification of specific alleles method) and performed serum iron studies in randomly selected English male blood donors (<4 previous units donated) in four age bands <30, 30-40, 40-50 and >50 years. Results: In 6261 subjects, frequency of C282Y homozygosity (+/+) was 0.3%, C282Y/H63D compound heterozygosity (+/-) 2.0%, and H63D and C282Y heterozygosity +/-, 21.7 and 10.4%, respectively. Genotype distribution was within Hardy-Weinberg equilibrium in each age band. C282Y +/- frequency fell from 11.7% in subjects <30 years to 8.2% in subjects >50 (Chi(2) 7.19; P < 0.005). No such trend was seen for C282Y + /+. In C282Y + /+ subjects, median serum ferritin was 247 (range 60-2449) mug/l and exceeded >500 mug/l in only two of 18 subjects. Compared to wild/wild (-/-) subjects, C282Y and H63D +/- subjects had slightly higher serum iron and lower unsaturated iron binding concentrations, similar overall serum ferritin values but higher serum ferritin values in subjects who had previously donated blood. Conclusions: C282Y + /+ shows limited biochemical expression and no trend towards age-related attrition. C282Y and H63D +/- may protect against iron deficiency. (C) 2003 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.