A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation.
OBJECTIVE
Two major mutations are defined within the hemochromatosis gene, HFE. Although the effects of the C282Y mutation have been well characterized, the effects of the H63D mutation remain unclear. We accessed a well-defined population in Busselton, Australia, and determined the frequency of the H63D mutation and its influence on total body iron stores.


METHODS
Serum transferrin saturation and ferritin levels were correlated with the H63D mutation in 2531 unrelated white subjects who did not possess the C282Y mutation.


RESULTS
Sixty-two subjects (2.1%) were homozygous for the H63D mutation, 711 (23.6%) were heterozygous, and 1758 (58.4%) were wild-type for the H63D mutation. Serum transferrin saturation was significantly increased in male and female H63D homozygotes and heterozygotes compared with wild-types. Serum ferritin levels within each gender were not influenced by H63D genotypes. Elevated transferrin saturation > or = 45% was observed in a greater proportion of male H63D carriers than male wild-types. Male H63D homozygotes (9%) and heterozygotes (3%) were more likely to have both elevated transferrin saturation and elevated ferritin > or = 300 ng/mL than male wild-types (0.7%). Homozygosity for H63D was not associated with the development of clinically significant iron overload.


CONCLUSIONS
Presence of the H63D mutation results in a significant increase in serum transferrin saturation but does not result in significant iron overload. In the absence of the C282Y mutation, the H63D mutation is not clinically significant.
Gochee
Peter A
PA
Queensland Institute of Medical Research and The University of Queensland, Brisbane, Western Australia.
Powell
Lawrie W
LW
Cullen
Digby J
DJ
Du Sart
Desiree
D
Rossi
Enrico
E
Olynyk
John K
JK
D000328:Adult; D000368:Aged; D005260:Female; D005293:Ferritins / Q000097:blood; D005787:Gene Frequency; D005820:Genetic Testing; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D017354:Point Mutation; D015995:Prevalence; D012680:Sensitivity and Specificity; D014168:Transferrin / Q000378:metabolism
C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D005293:Ferritins