Association study of polymorphisms in FOXO3, AKT1 and IGF-2R genes with human longevity in a Han Chinese population

// Ning Li 1,2,3,* , Huaichao Luo 1,3,* , Xiaoqi Liu 1,3 , Shi Ma 1,3 , He Lin 1,3 , Rong Chen 1,3 , Fang Hao 1,3 and Dingding Zhang 1,4 1 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 2 Department of Immunology, Zunyi Medical College, Zunyi, Guizhou, China 3 Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China 4 Department of Health Management, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China * These authors have contributed equally to this work Correspondence to: Dingding Zhang, email: // Keywords : human longevity, FOXO3, AKT1, IGF-2R, single nucleotide polymorphism (SNP), Gerotarget Received : July 01, 2015 Accepted : November 23, 2015 Published : December 16, 2015 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.