Association of mutations in the hemochromatosis gene with shorter life expectancy

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.
Original languageEnglish
JournalArchives of Internal Medicine
Volume161
Issue number20
Pages (from-to)2441-2444
Number of pages3
ISSN0003-9926
DOIs
Publication statusPublished - 12. Nov 2001

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Hemochromatosis
Life Expectancy
Mutation
Heterozygote
Population
Mutation Rate
Denmark
Longitudinal Studies
Age Groups

Keywords

  • Age Distribution
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Denmark
  • Diseases in Twins
  • Female
  • Gene Frequency
  • Genetic Screening
  • Genotype
  • HLA Antigens
  • Hemochromatosis
  • Heterozygote
  • Heterozygote Detection
  • Histocompatibility Antigens Class I
  • Humans
  • Life Expectancy
  • Longitudinal Studies
  • Male
  • Membrane Proteins
  • Middle Aged
  • Mutation
  • Population Surveillance

Cite this

@article{b01dfe70cdc511dd9908000ea68e967b,
title = "Association of mutations in the hemochromatosis gene with shorter life expectancy",
abstract = "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.",
keywords = "Age Distribution, Age Factors, Aged, Aged, 80 and over, Denmark, Diseases in Twins, Female, Gene Frequency, Genetic Screening, Genotype, HLA Antigens, Hemochromatosis, Heterozygote, Heterozygote Detection, Histocompatibility Antigens Class I, Humans, Life Expectancy, Longitudinal Studies, Male, Membrane Proteins, Middle Aged, Mutation, Population Surveillance",
author = "L Bathum and L Christiansen and H Nybo and Ranberg, {K A} and D Gaist and B Jeune and Petersen, {N E} and J Vaupel and Kaare Christensen",
year = "2001",
month = "11",
day = "12",
doi = "10.1001/archinte.161.20.2441",
language = "English",
volume = "161",
pages = "2441--2444",
journal = "Archives of Internal Medicine",
issn = "0003-9926",
publisher = "The JAMA Network",
number = "20",

}

Association of mutations in the hemochromatosis gene with shorter life expectancy. / Bathum, L; Christiansen, L; Nybo, H; Ranberg, K A; Gaist, D; Jeune, B; Petersen, N E; Vaupel, J; Christensen, Kaare.

In: Archives of Internal Medicine, Vol. 161, No. 20, 12.11.2001, p. 2441-2444.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Association of mutations in the hemochromatosis gene with shorter life expectancy

AU - Bathum, L

AU - Christiansen, L

AU - Nybo, H

AU - Ranberg, K A

AU - Gaist, D

AU - Jeune, B

AU - Petersen, N E

AU - Vaupel, J

AU - Christensen, Kaare

PY - 2001/11/12

Y1 - 2001/11/12

N2 - 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.

AB - 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.

KW - Age Distribution

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Denmark

KW - Diseases in Twins

KW - Female

KW - Gene Frequency

KW - Genetic Screening

KW - Genotype

KW - HLA Antigens

KW - Hemochromatosis

KW - Heterozygote

KW - Heterozygote Detection

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Life Expectancy

KW - Longitudinal Studies

KW - Male

KW - Membrane Proteins

KW - Middle Aged

KW - Mutation

KW - Population Surveillance

U2 - 10.1001/archinte.161.20.2441

DO - 10.1001/archinte.161.20.2441

M3 - Journal article

C2 - 11700156

VL - 161

SP - 2441

EP - 2444

JO - Archives of Internal Medicine

JF - Archives of Internal Medicine

SN - 0003-9926

IS - 20

ER -