Genetic associations with human longevity at the APOE and ACE loci.
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.
Schächter
F
F
Centre d'Etude du Polymorphisme Humain, Paris, France.
Faure-Delanef
L
L
Guénot
F
F
Rouger
H
H
Froguel
P
P
Lesueur-Ginot
L
L
Cohen
D
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012727:Sex Characteristics
D001057:Apolipoproteins E; D007703:Peptidyl-Dipeptidase A