title: Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis.
abstract: Numerous studies have shown associations between the FOXO3A gene, encoding the forkhead box O3 transcription factor, and human or specifically male longevity. However, the associations of specific FOXO3A polymorphisms with longevity remain inconclusive. We performed a meta-analysis of existing studies to clarify these potential associations. A comprehensive search was conducted to identify studies of FOXO3A gene polymorphisms and longevity. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by comparing the minor and major alleles. A total of seven articles reporting associations of FOXO3A polymorphisms with longevity were identified and included in this meta-analysis. These comprised 11 independent studies with 5241 cases and 5724 controls from different ethnic groups. rs2802292, rs2764264, rs13217795, rs1935949 and rs2802288 polymorphisms were associated with human longevity (OR = 1.36, 95% CI = 1.10-1.69, P= 0.005; OR = 1.20, 95% CI = 1.04-1.37, P= 0.01; OR = 1.27, 95% CI = 1.10-1.46, P= 0.001; OR = 1.14, 95% CI = 1.01-1.27 and OR = 1.24, 95% CI = 1.07-1.43, P= 0.003, respectively). Analysis stratified by gender indicated significant associations between rs2802292, rs2764264 and rs13217795 and male longevity (OR = 1.54, 95% CI = 1.33-1.79, P < 0.001; OR = 1.38, 95% CI = 1.15-1.66, P= 0.001; and OR = 1.39, 95% CI = 1.15-1.67, P= 0.001), but rs2802292, rs2764264 and rs1935949 were not linked to female longevity. Moreover, our study showed no association between rs2153960, rs7762395 or rs13220810 polymorphisms and longevity. In conclusion, this meta-analysis indicates a significant association of five FOXO3A gene polymorphisms with longevity, with the effects of rs2802292 and rs2764264 being male-specific. Further investigations are required to confirm these findings.
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Bao
authors.forename: Xian-Lu
authors.initials: XL
authors.lastname: Song
authors.forename: Ying-Qia
authors.initials: YQ
authors.lastname: Hong
authors.forename: Hai-Li
authors.initials: HL
authors.lastname: Zhu
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Urology and Medical Center for Overseas Patients, Nanfang Hospital, Guangzhou, China.
authors.forename: Shan-Chao
authors.initials: SC
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
mesh_terms: D016022:Case-Control Studies; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors