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Article
Nature Genetics  6, 29 - 32 (1994)
doi:10.1038/ng0194-29

Genetic associations with human longevity at the APOE and ACE loci

François Schächter1, Laurence Faure-Delanef1, Frédérique Guénot1, Hervé Rouger1, Philippe Froguel1, Laurence Lesueur-Ginot1 & Daniel Cohen1

1Centre d'Etude du Polymorphisme Humain, 27 rue Juliette Dodu, 75010 Paris, France

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 epsilon4 allele of APOE, which promotes premature atherosclerosis, is significantly less frequent in centenarians than in controls (p<0.001), while the frequency of the epsilon2 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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EISSN: 1546-1718
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