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Association of Mutations in the Hemochromatosis Gene With Shorter Life Expectancy
Lise Bathum, MD, PhD;
Lene Christiansen, PhD;
Hanne Nybo, MD;
Karen Andersen Ranberg, MD;
David Gaist, MD, PhD;
Bernard Jeune, MD;
Niels Erik Petersen, MD, PhD;
James Vaupel, PhD;
Kaare Christensen, MD, PhD
Arch Intern Med. 2001;161:2441-2444.
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 mutation—the mutation
most often associated with hereditary hemochromatosis—was 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.
From the Department of Clinical Biochemistry, University Hospital,
Odense, Denmark (Drs Bathum, Christiansen, and Petersen); The Danish Center
for Demographic Research and Epidemiology, Institute of Public Health, University
of Southern Denmark, Odense (Drs Nybo, Andersen Ranberg, Gaist, Jeune, Vaupel,
and Christensen); the Max Planck Institute for Demographic Research, Rostock,
Germany (Dr Vaupel); and the Terry Stanford Institute, Duke University, Durham,
NC (Drs Vaupel and Christensen).
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