Identification of rare and common variants of SIRT6 gene in long-lived individuals

Abstract

Objective SIRT6, a member of sirtuin family, is a candidate gene of longevity. This study aimed to investigate rare and common variants of the SIRT6 gene in long-lived individuals. Methods Overall 102 long-lived individuals aged 95 years and older were randomly sampled from the longevity group of the Rugao Longevity and Aging Study (RuLAS). The promoter and exon regions of the SIRT6 gene were amplified and sequenced to identify rare and common variants. The allele frequencies of variants in study subjects were compared with those in Han Chinese population in the 1000 Genome Project. Results Approximately 10 kb of the SIRT6 gene regions were sequenced, which covered all the 8 exons and 1.5 kb promoter. Twenty reported variants were identified in the study participants, including six variants in promoter, one variant in exons, two variants in 3′UTR, and eleven variants in introns. There were twelve reported variants with minor allele frequencies (MAFs) over 0.05, with rs352493 (MAF=0.245) being the a nonsynonymous variant. Within the 8 variants with MAF <0.05, we observed significant differences in allele frequencies of rs117541451 (MAF=0.010) and rs146420357 (MAF=0.029) in the study participants, compared to the Han Chinese population in the 1000 Genome Project (P=0.021). Five novel and rare variants (MAF=0.005) were identified in this study, including one variant in exons, one in promoter, one in 3′UTR, and two in introns. Conclusion Overall, we observed twenty reported (twelve common) and five novel (rare) variants in long-lived individuals in Rugao. Our results provide critical candidate variants for further genetic and functional research in longevity, and underscore the importance of rare variants promoting longevity. Key words: SIRT6; Rare variant; Common variant; Longevity