Association of the insulin-like growth factor binding protein 3 (IGFBP-3) polymorphism with longevity in Chinese nonagenarians and centenarians.
Association of the insulin-like growth factor binding protein 3 (IGFBP-3) polymorphism with longevity in Chinese nonagenarians and centenarians.
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DOI：
10.18632/aging.100703
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Kong QP
中科院分区：
文献类型：
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作者：
He YH;Lu X;Yang LQ;Xu LY;Kong QP
人类的寿命在很大程度上取决于遗传因素，一些研究已经确定了与人类寿命有关的假定基因。虽然一些基因位点与长寿有关，但由于种族差异，大多数基因位点难以复制。在这项研究中，我们使用基因组实验室的SNPstream基因分型系统，分析了1075个样本中18个基因单核苷酸多态性（snp）与寿命的关系，这些样本包括567名百岁老人和508名年轻的对照组。我们的研究结果证实了叉头箱O3 （FOXO3）变异（rs13217795）和ATM丝氨酸/苏氨酸激酶（ATM）变异（rs189037）基因型与寿命的相关性（p=0.0075和p=0.026，分别使用共显性模型和隐性模型）。值得注意的是，我们首次揭示了胰岛素样生长因子结合蛋白3 （IGFBP-3）基因多态性rs11977526与中国百岁老人/百岁老人寿命的关联（使用显性模型p=0.033，使用过显性模型p=0.035）。FOXO3和IGFBP-3是参与人类长寿的胰岛素/胰岛素样生长因子-1信号通路（IGF-1）的重要组成部分，而ATM基因参与感知DNA损伤和减少氧化应激，因此我们的研究结果强调了胰岛素通路和氧化应激在中国人群长寿中的重要作用。
Human lifespan is determined greatly by genetic factors and some investigations have identified putative genes implicated in human longevity. Although some genetic loci have been associated with longevity, most of them are difficult to replicate due to ethnic differences. In this study, we analyzed the association of 18 reported gene single nucleotide polymorphisms (SNPs) with longevity in 1075 samples consisting of 567 nonagenarians/centenarians and 508 younger controls using the GenomeLab SNPstream Genotyping System. Our results confirm the association of the forkhead box O3 (FOXO3) variant (rs13217795) and the ATM serine/threonine kinase (ATM) variant (rs189037) genotypes with longevity (p=0.0075 and p=0.026, using the codominant model and recessive model, respectively). Of note is that we first revealed the association of insulin-like growth factor binding protein 3 (IGFBP-3) gene polymorphism rs11977526 with longevity in Chinese nonagenarians/centenarians (p=0.033 using the dominant model and p=0.035 using the overdominant model). The FOXO3 and IGFBP-3 form important parts of the insulin/insulin-like growth factor-1 signaling pathway (IGF-1) implicated in human longevity, and the ATM gene is involved in sensing DNA damage and reducing oxidative stress, therefore our results highlight the important roles of insulin pathway and oxidative stress in the longevity in the Chinese population.