Department of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing, China.
Hum Mol Genet. 2009 Dec 15;18(24):4897-904. doi: 10.1093/hmg/ddp459. Epub 2009 Sep 29.
FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German and Italian populations. Here we tested the genetic contribution of FOXO1A and FOXO3A to the longevity phenotype in Han Chinese population. Six tagging SNPs from FOXO1A and FOXO3A were selected and genotyped in 1817 centenarians and younger individuals. Two SNPs of FOXO1A were found to be associated with longevity in women (P = 0.01-0.005), whereas all three SNPs of FOXO3A were associated with longevity in both genders (P = 0.005-0.001). One SNP from FOXO1A was found not to be associated with longevity. In haplotype association tests, the OR (95% CI) for haplotypes TTG and CCG of FOXO1A in association with female longevity were 0.72 (0.58-0.90) and 1.38 (1.08-1.76), P = 0.0033 and 0.0063, respectively. The haplotypes of FOXO3A were associated with longevity in men [GTC: OR (95% CI) = 0.67 (0.51-0.86), P = 0.0014; CGT: OR (95% CI) = 1.48 (1.12-1.94), P = 0.0035] and in women [GTC: OR (95% CI) = 0.75 (0.60-0.94), P = 0.0094; CGT: OR (95% CI) = 1.47 (1.16-1.86), P = 0.0009]. The haplotype association tests were validated by permutation analysis. The association of FOXO1A with female longevity was replicated in 700 centenarians and younger individuals that were sampled geographically different from the original population. Thus, we demonstrate that, unlike FOXO3A, FOXO1A is more closely associated with human female longevity, suggesting that the genetic contribution to longevity trait may be affected by genders.
FOXO1A 和 FOXO3A 是 FoxO 家族的两个成员。FOXO3A 最近与日本、德国和意大利人群的人类长寿有关。在这里，我们测试了 FOXO1A 和 FOXO3A 对汉族人群长寿表型的遗传贡献。从 FOXO1A 和 FOXO3A 中选择了 6 个标记 SNP，并在 1817 名百岁老人和年轻个体中进行了基因分型。发现 FOXO1A 的两个 SNP 与女性长寿相关（P = 0.01-0.005），而 FOXO3A 的三个 SNP 均与两性长寿相关（P = 0.005-0.001）。一个来自 FOXO1A 的 SNP 与长寿无关。在单体型关联测试中，与女性长寿相关的 FOXO1A 的单体型 TTG 和 CCG 的 OR（95%CI）分别为 0.72（0.58-0.90）和 1.38（1.08-1.76），P = 0.0033 和 0.0063。FOXO3A 的单体型与男性长寿相关[GTC：OR（95%CI）=0.67（0.51-0.86），P = 0.0014；CGT：OR（95%CI）=1.48（1.12-1.94），P = 0.0035]和女性长寿相关[GTC：OR（95%CI）=0.75（0.60-0.94），P = 0.0094；CGT：OR（95%CI）=1.47（1.16-1.86），P = 0.0009]。单体型关联测试通过置换分析得到验证。FOXO1A 与女性长寿的关联在从原始人群中地理上不同的 700 名百岁老人和年轻个体中得到了复制。因此，我们证明与 FOXO3A 不同，FOXO1A 与人类女性长寿更为密切相关，这表明对长寿性状的遗传贡献可能受到性别的影响。
