Association Between Genetic Variations In The Insulin/Insulin-Like Growth Factor (Igf-1) Signaling Pathway And Longevity: A Systematic Review And Meta-Analysis.

Abstract

Some studies have shown that polymorphisms in the insulin growth factor-1 (IGF-1) signaling pathway genes could influence human longevity. However, the results of different studies are often inconsistent. Our aim was to investigate by systematic review and meta-analysis the association of the common polymorphisms defining the genetic variability of the IGF-1 signaling pathway associated with human longevity. Eleven studies investigating the association between the polymorphisms in the IGF-1 signaling pathway genes (IGF-1, IGF-1 receptor (IGF-1R), Forkhead box O3A (FOXO3A) and Silent mating type information regulation 1 (SIRT1)) and longevity were found and analyzed. The model-free approach was applied to meta-analyze these studies. No association was reported between the single nucleotide polymorphisms (SNPs) of IGF-1 and longevity in the available study. The meta-analysis of available data from four studies, showed a significant association with the IGF-1R polymorphism rs2229765, suggesting that subjects with the A-bearing genotype have greater chance of longevity. Concerning the five studies on FOXO3A SNPs, for the rs2764264 significant association with longevity was observed for C allele when only males were included in the analysis. Statistically significant results were obtained for other SNPs as well, i.e. rs2802292 ( G allele), rs9400239 and rs479744 (T and A alleles, respectively). For rs9400239 the association was observed in male long lived with a lower odds ratio than in centenarians while in rs479744 it was highlighted a significant association in centenarians. Concerning SIRT1, no association between the SNPs under study and longevity was observed in the only available report. Current findings suggest that both IGF-1R and FOXO3A polymorphisms could be associated with longevity. The high degree of between-study heterogeneity and the low number of available studies underline the need for further methodologically adequate analyses to confirm these evidences.