Lin Rong, Zhang Yunxia, Yan Dongjing, Liao Xiaoping, Wang Xianshou, Fu Yunxin, Cai Wangwei
Department of Biology, Hainan Medical College, Haikou, Hainan, China.
Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, Hainan, China.
PLoS One. 2016 Dec 9;11(12):e0167918. doi: 10.1371/journal.pone.0167918. eCollection 2016.
Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. No nominally significant effects were found. However, when stratifying by gender, four SNPs (rs10499051, rs7762395, rs4946933 and rs3800230) previously reported to be associated with longevity and one novel SNP (rs4945815) showed significant association with male longevity (P-values: 0.007-0.032), but all SNPs were not associated with female longevity. Correspondingly, males carrying the G-G-T-G haplotype of rs10499051, rs7762395, rs4945815 and rs3800230 tended to have longer lifespan than those carrying the most common haplotype A-G-C-T (odds ratio = 2.36, 95% confidence interval = 1.20-4.63, P = 0.013). However, none of the associated SNPs and haplotype remained significant after Bonferroni correction. In conclusion, our findings revealed that the FOXO3 variants we tested in our population of Chinese men and women were associated with longevity in men only. None of these associations passed Bonferroni correction. Bonferroni correction is very stringent for association studies. We therefore believe the effects of these nominally significant variants on human longevity will be confirmed by future studies.
近期研究表明，叉头框O3（FOXO3）作为胰岛素/胰岛素样生长因子-1信号通路的关键调节因子，影响衰老和寿命。本研究旨在全面阐明中国人群中FOXO3常见基因变异与人类长寿的关联。在616名无亲缘关系的长寿个体和846名年轻对照中成功对FOXO3的18个单核苷酸多态性（SNP）进行了基因分型。未发现名义上显著的影响。然而，按性别分层时，先前报道与长寿相关的4个SNP（rs10499051、rs7762395、rs4946933和rs3800230）以及1个新的SNP（rs4945815）与男性长寿显著相关（P值：0.007 - 0.032），但所有SNP均与女性长寿无关。相应地，携带rs10499051、rs7762395、rs4945815和rs3800230的G - G - T - G单倍型的男性往往比携带最常见单倍型A - G - C - T的男性寿命更长（优势比 = 2.36，95%置信区间 = 1.20 - 4.63，P = 0.013）。然而，经Bonferroni校正后，所有相关的SNP和单倍型均不再显著。总之，我们的研究结果表明，我们在中国男性和女性群体中测试的FOXO3变异仅与男性长寿相关。这些关联均未通过Bonferroni校正。Bonferroni校正对于关联研究非常严格。因此，我们相信这些名义上显著的变异对人类长寿的影响将在未来的研究中得到证实。
