Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations
Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations
复制标题
FOXO1A 和 FOXO3A 与中国汉族人群长寿特征的遗传关联。
DOI：
10.1093/hmg/ddp459
复制
发表时间：
2009-12-15
影响因子：
3.5
通讯作者：
Tian, Xiao-Li
中科院分区：
文献类型：
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作者：
Li, Yang;Wang, Wen-Jing;Tian, Xiao-Li
FOXO1a和FOXO3a是FOXO家族的两名成员。最近，在日本、德国和意大利的人群中，FOXO3a被认为与人类长寿有关。在此，我们测试了FOXO1a和FOXO3a对中国汉族人群长寿表型的遗传贡献。从FOXO1a和FOXO3a中选取6个标记SNPs，对1817名百岁及以下人群进行基因分型。FOXO1a的两个SNPs与女性的长寿相关(P=0.005)，而FOXO3a的三个SNPs与女性的长寿有关(P=0.005-0.001)。来自FOXO1A的一个SNP被发现与长寿无关。在单倍型关联检验中，FOXO1ATTG和CCG单倍型与女性长寿的OR值分别为0.72(0.58~0.90)和1.38(1.08~1.76)，P=0.0033和0.0063。FOXO3a单倍型与男性[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[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]相关。单倍型关联检验通过排列分析进行验证。FOXO1a与女性寿命的关联在700名百岁老人和更年轻的人中得到了复制，这些人是在不同地理位置的原始人群中进行抽样的。因此，我们证明，与FOXO3a不同，FOXO1a与人类女性寿命更密切相关，这表明对长寿性状的遗传贡献可能受到性别的影响。
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.