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 bysystematic review and meta-analysis the association of the common polymorphismsdefining the genetic variability of the IGF-1 signaling pathway associated withhuman longevity. Eleven studies investigating the association between thepolymorphisms in the IGF-1 signaling pathway genes (IGF-1, IGF-1 receptor(IGF-1R), Forkhead box O3A (FOXO3A) and Silent mating type information regulation1 (SIRT1)) and longevity were found and analyzed. The model-free approach wasapplied to meta-analyze these studies. No association was reported between thesingle nucleotide polymorphisms (SNPs) of IGF-1 and longevity in the availablestudy. The meta-analysis of available data from four studies, showed asignificant association with the IGF-1R polymorphism rs2229765, suggesting thatsubjects with the A-bearing genotype have greater chance of longevity. Concerningthe five studies on FOXO3A SNPs, for the rs2764264 significant association withlongevity was observed for C allele when only males were included in theanalysis. 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 witha lower odds ratio than in centenarians while in rs479744 it was highlighted asignificant association in centenarians. Concerning SIRT1, no association betweenthe SNPs under study and longevity was observed in the only available report.Current findings suggest that both IGF-1R and FOXO3A polymorphisms could beassociated with longevity. The high degree of between-study heterogeneity and thelow number of available studies underline the need for further methodologicallyadequate analyses to confirm these evidences.
|Numero di pagine||8|
|Rivista||Current Vascular Pharmacology|
|Stato di pubblicazione||Published - 2014|
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