Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations.
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.
Department of Human Population Genetics, Institute of Molecular Medicine, Peking University, Beijing, China.
Yang
Y
Li
Wen-Jing
WJ
Wang
Huiqing
H
Cao
Jiehua
J
Lu
Chong
C
Wu
Fang-Yuan
FY
Hu
Jian
J
Guo
Ling
L
Zhao
Fan
F
Yang
Yi-Xin
YX
Zhang
Wei
W
Li
Gu-Yan
GY
Zheng
Hanbin
H
Cui
Xiaomin
X
Chen
Zhiming
Z
Zhu
Hongbo
H
He
Birong
B
Dong
Xianming
X
Mo
Yi
Y
Zeng
Xiao-Li
XL
Tian
D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002681:China; D005260:Female; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors
C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors