Expression of the HFE hemochromatosis gene in a community-based population of elderly women.
OBJECTIVE
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.


CONCLUSIONS
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.
Rossi
Enrico
E
Department of Clinical Biochemistry, PathCentre Western Australian Centre for Pathology and Medical Research, Nedlands, Western Australia, Australia. ric.rossi@health.wa.gov.au
Kuek
Conchita
C
Beilby
John P
JP
Jeffrey
Gary P
GP
Devine
Amanda
A
Prince
Richard L
RL
D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D019683:Penetrance; D012111:Residence Characteristics
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D005293:Ferritins