Schächter F, Faure-Delanef L, Guénot F, Rouger H, Froguel P, Lesueur-Ginot L, Cohen D
Centre d'Etude du Polymorphisme Humain, Paris, France.
Nat Genet. 1994 Jan;6(1):29-32. doi: 10.1038/ng0194-29.
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.
为了剖析长寿的遗传成分，我们在几个多态性候选基因位点对百岁老人群体（n = 338）和20 - 70岁的成年人进行了病例对照研究。在此，我们报告了对两个基因的研究结果，这两个基因因其对心血管风险的影响而被选中，分别编码载脂蛋白E（ApoE）和血管紧张素转换酶（ACE）。我们发现，促进动脉粥样硬化过早发生的APOE的ε4等位基因在百岁老人中的频率显著低于对照组（p < 0.001），而先前与III型和IV型高脂血症相关的ε2等位基因的频率则显著增加（p < 0.01）。令人惊讶的是，一种易患冠心病的ACE变体在百岁老人中更为常见，纯合基因型显著增加（p < 0.01）。这些关联提供了遗传因素对不同生存情况影响的实例，并可能指向对长寿的多效性年龄依赖性效应。
