Abstract
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.
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Acknowledgements
We thank Mrs W Luijten for HFE genotyping and Dr HJM Smeets for providing reference samples. This study was supported by the Netherlands Organization for Scientific Research (NWO), the Netherlands Diabetes Foundation, the NESTOR Stimulation Program for Geriatric Research in The Netherlands (Ministry of Health and Ministry of Education) and the Municipality of Rotterdam. Dr Osborne's position has been funded by a National Health and Medical Research Council of Australia Public Health Fellowship.
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Njajou, O., Houwing-Duistermaat, J., Osborne, R. et al. A population-based study of the effect of the HFE C282Y and H63D mutations on iron metabolism. Eur J Hum Genet 11, 225–231 (2003). https://doi.org/10.1038/sj.ejhg.5200955
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DOI: https://doi.org/10.1038/sj.ejhg.5200955
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