title: Association study of polymorphisms in FOXO3, AKT1 and IGF-2R genes with human longevity in a Han Chinese population.
abstract: FOXO3, AKT1 and IGF-2R are critical members of the insulin/IGF-1 signaling pathway. Previous studies showed that polymorphisms (SNPs) in FOXO3, AKT1 and IGF-2R were associated with human longevity in Caucasian population. However, the association of these SNPs in different ethnic groups is often inconsistent. Here, we investigated the association of genetic variants in three genes with human longevity in Han Chinese population. Twelve SNPs from FOXO3, AKT1 and IGF-2R were selected and genotyped in 1202 long-lived individuals (nonagenarians and centenarians) and younger individuals. Rs9486902 of FOXO3 was found to be associated with human longevity in both genders combined in this study (allelic P = 0.002, corrected P = 0.024). The other eleven SNPs were not significantly associated with human longevity in Han Chinese population. The haplotypes TTCTT, CCTTC and CTCCT of FOXO3 as well as GGTCGG and GGTCAG of AKT1 were shown to have a significant difference between case and control (P =0.006, 2.78×10-5, 4.68×10-6, 0.003,0.005, respectively). The estimated prevalence of diabetes and prediabetes in long-lived individuals was significantly lower than in common adult populations (P = 0.001, 2.3×10-26) .Therefore, the search for longevity-associated genes provides the identification of new potential targets beneficial for the treatment of diabetes.
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, the Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.|Department of Immunology, Zunyi Medical College, Zunyi, Guizhou, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, the Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
authors.forename: Huaichao
authors.initials: H
authors.lastname: Luo
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, the Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, the Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Ma
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, the Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
authors.forename: He
authors.initials: H
authors.lastname: Lin
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, the Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, the Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.|Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hao
authors.affiliation: Sichuan Provincial Key Laboratory for Human Disease Gene Study, the Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.|Department of Health Management, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000208:ethnology / Q000235:genetics; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008136:Longevity / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011236:Prediabetic State / Q000208:ethnology / Q000235:genetics; D015995:Prevalence; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D017527:Receptor, IGF Type 2; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT1; FOXO3; Gerotarget; IGF-2R; human longevity; single nucleotide polymorphism (SNP)