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

Abstract

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) μg/l and exceeded >500 μg/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.