Genetic associations with human longevity at the APOE and ACE loci.

Authors: Schächter F; Faure-Delanef L; Guénot F; Rouger H; Froguel P; Lesueur-Ginot L; Cohen D

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.

Keywords: Adult; Aged; Aged, 80 and over; Alleles; Apolipoproteins E/*genetics; Base Sequence; Case-Control Studies; Female; France/epidemiology; Gene Frequency; Genotype; Humans; Longevity/*genetics; Male; Middle Aged; Molecular Sequence Data; Peptidyl-Dipeptidase A/*genetics; Polymorphism, Genetic; Sex Characteristics
Journal: Nature genetics
Volume: 6
Issue: 1
Pages: 29-32
Date: Jan. 1, 1994
PMID: 8136829
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Schächter F, Faure-Delanef L, Guénot F, Rouger H, Froguel P, Lesueur-Ginot L, Cohen D (1994) Genetic associations with human longevity at the APOE and ACE loci. Nature genetics 6: 29-32.

Lifespan Factors:
  • ACE angiotensin I converting enzyme (peptidyl-dipeptidase A) 1
  • APOE apolipoprotein E

  • Longevity Variant Associations (p-value):
  • APOE e2/e4 (0.001)
  • rs4340 (0.001)

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