Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations

Abstract

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.

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

“…(2009) analyzed six SNPs from FOXO1A and FOXO3A genes by comparing 761 centenarians and 1056 younger individuals (control group) of the Han Chinese population. They found two SNPs of FOXO1A to be negatively associated with longevity in women, rs2755209 and rs2755213.…”

“…They found two SNPs of FOXO1A to be negatively associated with longevity in women, rs2755209 and rs2755213. On the other hand, all three SNPs studied for FOXO3A (rs2253310, rs2802292, and rs4946936) were positively associated with longevity in both genders (Li et al ., 2009). They have concluded that as FOXO1A is more strictly associated with human female longevity, the genetic contribution to longevity trait may be affected by genders (Li et al ., 2009).…”

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

“…However, two loci that are repeatedly found by GWAS of aging are APOE (Deelen et al, 2011; Ewbank, 2007; Gerdes, Jeune, Ranberg, Nybo, & Vaupel, 2000) and FOXO3A (Anselmi et al, 2009; Flachsbart et al, 2009; Li et al, 2009; Pawlikowska et al, 2009; Willcox et al, 2008). Similar to AD, APOE ε2 is found to be enriched in elderly and centenarians compared to younger individuals (Seripa et al, 2006).…”

Epigenetic regulation of aging stem cells

“…In invertebrates, FOXO transcription factors are important for longevity downstream of insulin signaling (Lin et al, 1997;Ogg et al, 1997;Giannakou et al, 2004;Hwangbo et al, 2004). Interestingly, polymorphisms in the FOXO3 gene are associated with extreme longevity in humans (Anselmi et al, 2009;Flachsbart et al, 2009;Li et al, 2009;Pawlikowska et al, 2009). In adult HSCs and NSCs, FOXO factors cooperate to regulate stem cell selfrenewal and homeostasis.…”