Background and aim: Recent studies suggest that the clinical penetrance of associated hereditary hemochromatosis, defined as either the C282Y homozygote or compound heterozygote HFE genotype status, is much lower than previously thought.
Methods: We investigated the clinical penetrance and phenotypic expression of HFE-associated hereditary hemochromatosis in a community-based population of 1352 elderly female subjects with a mean age of 75 years. Serum transferrin saturation and ferritin levels were determined on all subjects bearing a C282Y mutation and a subset of wild-type C282Y subjects.
Results: The prevalences of the C282Y homozygous and compound heterozygous HFE genotypes were 0.15% (2/1352) and 2.0% (27/1352), respectively. The observed prevalence of 0.15% for C282Y homozygotes borders on significance (P = 0.054) for deviation from the Hardy-Weinberg population equilibrium calculations, which predict a prevalence of 0.49%, whereas the observed and predicted compound heterozygote prevalences were not significantly different. Clinical symptoms of hemochromatosis were absent in both the C282Y homozygote subjects. Of the compound heterozygous subjects, 2/27 (7%) had elevated serum transferrin saturation and ferritin values; however, clinical symptoms of hemochromatosis were absent in both. Considered as a whole, the compound heterozygous subjects had markedly elevated means for serum iron (19.4 vs 16.0 micromol/L, P = 0.0008), transferrin saturation (34.8% vs 25.2%, P < 0.0001) and ferritin (157 vs 92 microg/L, P = 0.002) compared with the wild-type subjects.
Conclusion: The C282Y homozygous HFE hereditary hemochromatosis genotype was under-represented in this elderly cohort, whereas the compound heterozygous genotype was not. None of the homozygous or compound heterozygous subjects expressed the phenotype of iron overload disease.
Copyright 2004 Blackwell Publishing Asia Pty Ltd