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

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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

DOI 10.1038/ng0194-29

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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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Authors: Schächter, F., Faure-Delanef, L., Guénot, F., Rouger, H., Froguel, P., Lesueur-Ginot, L., & Cohen, D.
Affiliations: Fondation Jean Dausset-CEPH (FR)
ORCID: Froguel, Philippe
Cohen, Daniel
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 1994-01
Volume: 6
Issue: 1
Pages: 29-32
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng0194-29
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
Licence: www.springer.com/tdm (tdm)
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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Genetic associations with human longevity at the APOE and ACE loci

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