Genetic Association Analysis of Common Variants in FOXO3 Related to Longevity in a Chinese Population.
Genetic Association Analysis of Common Variants in FOXO3 Related to Longevity in a Chinese Population.
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中国人群长寿相关 FOXO3 常见变异的遗传关联分析
DOI：
10.1371/journal.pone.0167918
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Lin R;Zhang Y;Yan D;Liao X;Wang X;Fu Y;Cai W
近期研究表明，叉头框O3（FOXO3）是胰岛素/胰岛素样生长因子 - 1信号通路的关键调节因子，该通路影响衰老和寿命。本研究旨在全面阐明FOXO3常见基因变异与中国人群人类寿命的关联。在616名无亲缘关系的长寿个体和846名较年轻的对照者中，成功对FOXO3中的18个单核苷酸多态性（SNP）进行了基因分型。未发现有显著意义的影响。然而，按性别分层时，先前报道的与长寿相关的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与女性长寿均无关。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，在进行邦费罗尼校正后，所有相关的SNP和单倍型均不再显著。总之，我们的研究结果显示，我们在中国男性和女性人群中检测的FOXO3变异仅与男性长寿相关。这些关联均未通过邦费罗尼校正。邦费罗尼校正对于关联研究来说非常严格。因此，我们相信这些具有名义显著意义的变异对人类寿命的影响将在未来的研究中得到证实。
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.
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DOI：
10.18632/aging.100703
发表时间：
2014-11
期刊：
Aging
影响因子：
--
作者：
He YH;Lu X;Yang LQ;Xu LY;Kong QP
通讯作者：
Kong QP
影响因子：
7.8
作者：
Soerensen M;Dato S;Christensen K;McGue M;Stevnsner T;Bohr VA;Christiansen L
通讯作者：
Christiansen L
影响因子：
7.8
作者：
Pawlikowska L;Hu D;Huntsman S;Sung A;Chu C;Chen J;Joyner AH;Schork NJ;Hsueh WC;Reiner AP;Psaty BM;Atzmon G;Barzilai N;Cummings SR;Browner WS;Kwok PY;Ziv E;Study of Osteoporotic Fractures
通讯作者：
Study of Osteoporotic Fractures
影响因子：
5.8
作者：
Sole, Xavier;Guino, Elisabet;Moreno, Vitor
通讯作者：
Moreno, Vitor
影响因子：
10.4
作者：
Chen, X.;Li, S.;Wang, X.
通讯作者：
Wang, X.