title: Genetic Association Analysis of Common Variants in FOXO3 Related to Longevity in a Chinese Population.
abstract: 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.
authors.affiliation: Department of Biology, Hainan Medical College, Haikou, Hainan, China.
authors.forename: Rong
authors.identifier: http://orcid.org/0000-0001-9161-6844
authors.initials: R
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, Hainan, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, Hainan, China.
authors.forename: Dongjing
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Hainan Medical College, Haikou, Hainan, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liao
authors.affiliation: Specialized Biotechnologies Lab, Hainan Medical College, Haikou, Hainan, China.
authors.forename: Xianshou
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Biostatistics and Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.|Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan, China.
authors.forename: Yunxin
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, Hainan Medical College, Haikou, Hainan, China.
authors.forename: Wangwei
authors.initials: W
authors.lastname: Cai
mesh_terms: D016022:Case-Control Studies; D002681:China; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008136:Longevity / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3