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 ε4 allele of APOE, which promotes premature atherosclerosis, is significantly less frequent in centenarians than in controls (p<0.001), while the frequency of the ε2 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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Schächter, F., Faure-Delanef, L., Guénot, F. et al. Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 6, 29–32 (1994). https://doi.org/10.1038/ng0194-29
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DOI: https://doi.org/10.1038/ng0194-29