A population-based study of the effect of the HFE C282Y and H63D mutations on iron metabolism

Njajou, Omer T., Houwing-Duistermaat, Jeanine J., Osborne, Richard H., Vaessen, Norbert, Vergeer, Jeanette, Heeringa, Jan, Pols, Huibert A. P., Hofman, Albert and van Duijn, Cornelia M 2003, A population-based study of the effect of the HFE C282Y and H63D mutations on iron metabolism, European journal of human genetics, vol. 11, pp. 225-231, doi: 10.1038/sj.ejhg.5200955.

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Title A population-based study of the effect of the HFE C282Y and H63D mutations on iron metabolism
Author(s) Njajou, Omer T.
Houwing-Duistermaat, Jeanine J.
Osborne, Richard H.ORCID iD for Osborne, Richard H. orcid.org/0000-0002-9081-2699
Vaessen, Norbert
Vergeer, Jeanette
Heeringa, Jan
Pols, Huibert A. P.
Hofman, Albert
van Duijn, Cornelia M
Journal name European journal of human genetics
Volume number 11
Start page 225
End page 231
Total pages 7
Publisher Nature Publishing Group
Place of publication London, England
Publication date 2003
ISSN 1018-4813
Summary The C282Y and H63D mutations in the HFE gene are important causes of hemochromatosis. In the elderly, these mutations might be associated with increased morbidity because of the lifelong accumulation of iron. In a population-based sample of the elderly, we determined the value of genotyping for HFE mutations to screen for subclinical hemochromatosis. HFE genotype frequencies were determined in a random group of 2095 subjects (55 years and over). In this random group, we selected within the six genotype groups a total of 342 individuals and measured their serum transferrin saturation, iron and ferritin levels. We also estimated the heritability and parameters needed to evaluate screening, including the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of HFE genotypes. Iron parameters were significantly increased in subjects homozygous, heterozygous or compound heterozygous. The effect of the mutations was more pronounced in men than in women. For the H63D mutation, an allele dose effect was observed. The HFE gene explained about 5% of the variability in serum iron indices. The PPV for hemochromatosis for the C282Y homozygous was 100% in men and 67% in women. The NPV of the wild-type allele was 97% for both men and women. The sensitivity of both mutations was 70% for men and 52% for women and the specificity was 62% for men and 64% for women. Our study shows that the HFE C282Y and H63D are determinants of iron parameters in the elderly and will be effective in detecting individuals at high risk of hemochromatosis. However, when screening based on these two mutations, some individuals with subclinical hemochromatosis will be missed.
Language eng
DOI 10.1038/sj.ejhg.5200955
Field of Research 060499 Genetics not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2003, Nature Publishing Group
Persistent URL http://hdl.handle.net/10536/DRO/DU:30025453

Document type: Journal Article
Collection: School of Health and Social Development
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