Identification of single nucleotide polymorphisms in the p21 (CDKN1A) gene and correlations with longevity in the Italian population.

Aging
Silvia GravinaIgor B Roninson

Abstract

Longevity in humans is determined by multiple environmental and genetic factors. We have investigated possible associations between longevity and Single Nucleotide Polymorphisms (SNPs) in the p21 (CDKN1A) gene, a stress-inducible senescence-associated cell cycle inhibitor, expression of which upregulates genes implicated in several age-related diseases. By sequencing the promoter and exons of p21 in genomic DNA of ten individuals over 90 years old, we have identified 30 SNPs, many of which had not been previously characterized. A cluster of minor alleles within the -4547/-3489 bp region did not alter the basal activity or p53 responsiveness of the p21 promoter. We then compared the frequency of 41 p21 SNPs between 184 centenarians and 184 younger subjects in the Italian population. Rare alleles of two exon-derived SNPs, rs1801270 and rs1059234, were significantly under-represented among the centenarians; no significant differences were found for 39 non-exonic SNPs. SNP rs1801270 causes Ser to Arg substitution at amino acid 31 and SNP rs1059234 leads to a nucleotide change in the 3'-untranslated region. Previous studies showed that the rare alleles of these two SNPs may play a role in cancer. These p21 alleles may be potentially...Continue Reading

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Citations

Mar 16, 2011·The Journal of Clinical Investigation·Huabiao ChenMathias Lichterfeld
Sep 21, 2013·Carcinogenesis·Ivna Néria Silva Ribamar CarvalhoFernando Regla Vargas
Jan 20, 2017·Aging Cell·Estefania Carrasco-GarciaAnder Matheu
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Aug 17, 2010·Ageing Research Reviews·Wen-Hung ChungShuen-Iu Hung

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