Association of FOXO3A variation with human longevity confirmed in German centenarians
Association of FOXO3A variation with human longevity confirmed in German centenarians
复制标题
DOI：
10.1073/pnas.0809594106
复制
发表时间：
2009-02-24
影响因子：
11.1
通讯作者：
Nebel, Almut
中科院分区：
文献类型：
--
作者：
Flachsbart, Friederike;Caliebeb, Amke;Nebel, Almut
人类叉头框 O3A 基因 (FOXO3A) 编码一种进化上保守的胰岛素-IGF1 信号通路关键调节因子，已知该信号通路会影响模型生物体的新陈代谢和寿命。最近的一项研究描述了 FOXO3A 基因中的 3 个 SNP，这些 SNP 在日本血统长寿男性的发现样本中与长寿具有统计学显着相关性 [Willcox 等，2017]。 (2008)Proc Natl Acad Sci USA 105：13987-13992]。然而，这一发现需要在独立群体中进行复制。在这里，我们调查了 1,762 名德国百岁老人/九十岁老人和年轻对照者中的 16 个已知 FOXO3A SNP，并提供了证据，证明该基因的多态性确实与获得超常晚年的能力有关。 FOXO3A 关联在百岁老人中比在九十岁老人中显着更强，这凸显了百岁老人对于遗传长寿研究的重要性。我们的研究将在日本男性中观察到的初步发现扩展到女性，并表明两种性别可能同样受到 FOXO3A 变异的影响。在法国百岁老人样本中的复制产生了支持先前结果的趋势。我们的研究结果证实了日本样本中的初步发现，并表明 FOXO3A 是人类延长生存的易感基因。
The human forkhead box O3A gene (FOXO3A) encodes an evolutionarily conserved key regulator of the insulin-IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in a discovery sample of long-lived men of Japanese ancestry [Willcox et al. (2008) Proc Natl Acad Sci USA 105: 13987-13992]. However, this finding required replication in an independent population. Here, we have investigated 16 known FOXO3A SNPs in an extensive collection of 1,762 German centenarians/nonagenarians and younger controls and provide evidence that polymorphisms in this gene were indeed associated with the ability to attain exceptional old age. The FOXO3A association was considerably stronger in centenarians than in nonagenarians, highlighting the importance of centenarians for genetic longevity research. Our study extended the initial finding observed in Japanese men to women and indicates that both genders were likely to be equally affected by variation in FOXO3A. Replication in a French centenarian sample generated a trend that supported the previous results. Our findings confirmed the initial discovery in the Japanese sample and indicate FOXO3A as a susceptibility gene for prolonged survival in humans.