Cited by 1,095Genetic Associations and EpidemiologyGenetics, Aging, and Longevity in Model OrganismsParaoxonase enzyme and polymorphisms

Genetic associations with human longevity at the APOE and ACE loci

Schächter, François, Faure-Delanef, Laurence, Guénot, Frédérique, Rouger, Hervé, Froguel, Philippe, Lesueur-Ginot, Laurence, Cohen, Daniel·1994·Nature Genetics

Abstract

In an effort to dissect the genetic components of longevity, we have undertaken case-control studies of populations of centenarians (n = 338) and adults aged 20-70 years at several polymorphic candidate gene loci. Here we report results on two genes, chosen for their impact on cardiovascular risk, encoding apolipoprotein E (ApoE), angiotensin-converting enzyme (ACE). We find that the epsilon 4 allele of APOE, which promotes premature atherosclerosis, is significantly less frequent in centenarians than in controls (p < 0.001), while the frequency of the epsilon 2 allele, associated previously with type III and IV hyperlipidemia, is significantly increased (p < 0.01). A variant of ACE which predisposes to coronary heart disease is surprisingly more frequent in centenarians, with a significant increase of the homozygous genotype (p < 0.01). These associations provide examples of genetic influences on differential survival and may point to pleiotropic age-dependent effects on longevity.

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Crossref · 10.1038/ng0194-29

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Authors
Schächter, F., Faure-Delanef, L., Guénot, F., Rouger, H., Froguel, P., Lesueur-Ginot, L., & Cohen, D.
Affiliations
Fondation Jean Dausset-CEPH (FR)
Venue
Nature Genetics
Published
1994-01
Volume
6
Issue
1
Pages
29-32
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W2069863984
Cited by
1,095
References
36
Citations by year
2026: 11 · 2025: 15 · 2024: 17 · 2023: 14 · 2022: 22 · 2021: 18 · 2020: 26 · 2019: 30 · 2018: 22 · 2017: 29 · 2016: 33 · 2015: 28 · 2014: 33 · 2013: 27 · 2012: 33
FWCI
39.36
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
Keywords
human longevity, centenarians, apolipoprotein E, APOE ε4, angiotensin-converting enzyme, ACE I/D polymorphism, genetic association, atherosclerosis, coronary artery disease, cardiovascular risk, hyperlipidemia, pleiotropy, differential survival
MeSH terms
Adult, Aged, Aged, 80 and over, Alleles, Apolipoproteins E, Base Sequence, Female, France, Gene Frequency, Genotype, Humans, Peptidyl-Dipeptidase A, Longevity, Male, Middle Aged, Molecular Sequence Data, Polymorphism, Genetic, Sex Characteristics, Case-Control Studies

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