| 其他摘要 | With the worldwide increase of the aging population, more and more countries have to face the social and economic problems brought by the aging population. Scientists hope to elucidate the mechanisms of aging related diseases and find the treatment methods to them by focusing on aging and longevity researches. The ultimate aim is to decrease the risk of disease incidence and the social and economic burden. The longevity population, who succeed in escaping most of the aging related diseases, is an excellent model for aging and longevity researches and becomes a hotspot. On the other hand, the genetics of longevity gains more and more attentions for the relative high heritability of longevity. Insulin/IGF1 signaling pathway is a conserved pathway, which controls the growth and metabolism of organisms. In the researches on model animals, decreasing the signaling strength by mutation in the genes of this pathway can increase the life span of the animals. At the same time, in association studies in humans, scientists found that some genetic variations in the genes of this pathway are associated with serum IGF1 level, human longevity, and some aging related diseases such as diabetes, cancers and cardiovascular diseases. Therefore, we performed an association study in a Han Chinese population to quest the potential association between the genetic variations in genes of IIS pathway and longevity. In this study, 493 unrelated elderly individuals (age≥94 for female and age≥90 for male) were recruited from Dujiangyan in Sichuan province of China. Meanwhile, 442 control individuals, which were healthy local younger people, were recruited from the same area (age 22-73). We scanned the genetic variations in some genes of IIS pathway as follows: (1) the promoter region and a microsatellite site in intron 2 of IGF1 gene; (2) three SNPs and a 2bp deletion in exons of IGF1R gene; (3) three SNPs in intron1 of FOXO3A gene. Our results suggested that there are no associations between the genetic variations in IGF1 promoter region, intron 2 and IGF1R exons. However, there are more male individuals with 18/21 genotype of the microsatellite in IGF1 promoter region in longevity group than that in control group (11.11 vs. 5.45%, p=0.011). As the significance disappeared when corrected by Bonferroni’s method, considering that the microsatellite site was associated with many aging related diseases by many reports, we speculate that the 18/21 genotype can not be functional in longevity; however, it may link with the real functional site as there is a long haplotype block embracing the microsatellite locus. At the same time, our results confirmed that the genetic variations in FOXO3A gene were associated with longevity in a Han Chinese population, following the evidences in Japanese, Germany and Italian populations. Furthermore, we found a novel SNP in FOXO3A gene. The homozygotes of mutation allele of this SNP appear only in longevity groups (8/492 vs. 0/414, p=0.011). By our knowledge, it is the first time to report an association study of genetic variations in genes of IIS pathway and longevity. Future studies with more individuals in other populations will test our conclusions. |
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