HFE mutations, iron deficiency and overload in 10 500 blood donors

People with genetic haemochromatosis (GH) accumulate iron from excessive di etary absorption. In populations of northern European origin, over 90% of p atients are homozygous for the C282Y mutation of the HFE gene. While about 1 in 200 people in the general population have this genotype the proportion who develop clinical haemochromatosis is not known. The influence of HFE g enotype on iron status was investigated in 10 556 blood donors. The allele frequencies of the C282Y and H63D mutations were 8.23% and 15.3% respective ly. Heterozygosity for C282Y occurred in 1 in 7.9 donors, for H63D in 1 in 4.2 donors, and 1 in 42 were compound heterozygotes. Homozygosity for H63D occurred in I in 42 donors and I in 147 (72) were homozygous for C282Y Mean values increased for transferrin saturation (TS) and serum ferritin (sFn), and decreased for unsaturated iron binding capacity (UIBC) in the order: d onors lacking the mutations, H63D heterozygotes, C282Y heterozygotes, H63D homozygotes, compound heterozygotes. and C282Y homozygotes, but serum ferri tin (sFn) concentrations were no higher in H63D heterozygotes and C282Y het erozygous women than in donors lacking mutations. The percentage of donors failing the screening test for anaemia or of those with sFn < 15 <mu>g/l di d not differ among the genotype groups. C282Y and H63D heterozygotes and do nors homozygous for H63D were at no greater risk of iron accumulation than donors lacking mutations, of whom 1 in 1200 had both a raised TS and sFn. T he risk was higher for compound heterozygotes (1 in 80, P = 0.003) and for C282Y homozygotes (1 in 5, P < 0.0001). There was no correlation between sF n and either age or donation frequency in C282Y homozygotes. None of the 63 C282Y homozygous donors interviewed showed physical signs of overload or w ere aware of relatives with haemochromatosis. The Welsh Blood Service colle cts blood from about 140 000 people each year including an estimated 950 wh o are homozygous for HFE C282Y. They are probably healthy and unaware of an y family history of iron overload.