Association of mutations in the hemochromatosis gene with shorter life expectancy.
Archives of Internal Medicine, 161:20, 2441–2444 (2001)
Background To investigate whether the frequency of carriers of mutations in the HFE gene associated with hereditary hemochromatosis diminishes with age as an indication that HFE mutations are associated with increased mortality. It is of value in the debate concerning screening for hereditary hemochromatosis to
determine the significance of heterozygosity.
Methods Genotyping for mutations in exons 2 and 4 of the HFE gene using denaturing gradient gel electrophoresis in 1784 participants aged 45 to 100 years from 4 population-based studies: all 183 centenarians from the Danish Centenarian Study, 601 people aged 92 to 93 years from the Danish 1905 Cohort, 400 aged 70 to 94 years from the Longitudinal Study of Aging Danish Twins, and 600 aged 45 to 67 years from a study of middle-aged Danish twins.
Results All participants (N=1784) were screened for mutations in exon 4, and a trend toward fewer heterozygotes for the C282Y mutationthe mutation most often associated with hereditary hemochromatosiswas found. This was significant for the whole population (P=.005) and for women (P=.004) but not for men (P=.26). A group of 599 participants was screened for mutations in exon 2, and there was no variation in the distribution of mutations in exon 2 in the different age groups.
Conclusions In a high–carrier frequency population like Denmark, mutations in HFE show an age-related reduction in the frequency of heterozygotes for C282Y, which suggests that carrier status is associated with shorter life expectancy. (© 2001 AMERICAN MEDICAL ASSOCIATION)