The common germline Arg72Pro polymorphism of p53 and increased longevity in humans

TY - JOUR

T1 - The common germline Arg72Pro polymorphism of p53 and increased longevity in humans

AU - Bojesen, S.E.

AU - Nordestgaard, Børge

N1 - Times Cited: 1ArticleEnglishBojesen, S. EUniv Copenhagen, Herlev Hosp, Dept Clin Biochem, Herlev Ringvej 75, DK-2730 Herlev, DenmarkCited References Count: 47266OSLANDES BIOSCIENCE1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USAAUSTIN

PY - 2008

Y1 - 2008

N2 - More than ten million single nucleotide polymorphisms ( SNPs) have been identified in humans; however, the importance of most SNPs for health and disease is not understood. Most SNPs are indeed unimportant and because of often inadequately powered studies, many observations on SNP effects can not be repeated by other researchers. SNPs are at best shown to influence protein function or level, rarely to influence risk of disease, and almost never to influence total mortality, the ultimate endpoint. A well-known functional SNP in the tumor suppressor TP53 gene leads to increased longevity: in the Danish general population (n = 9219) homozygotes for the minor allele versus homozygotes for the major allele had an increase in median survival of 3 years. This is partly explained by increased survival after development of cancer or other diseases, in accordance with the observation that this Arg72Pro substitution in the p53 protein has important influence on cell death via increased apoptosis. Thus, the increased longevity may be due to a generally increased robustness after a diagnosis of any life-threatening disease. In contrast to widespread skepticism on the importance of SNPs in humans, this gain-of-function p53 SNP of importance for cell repair mechanisms has a profound influence on longevity Udgivelsesdato: 2008/1/15

AB - More than ten million single nucleotide polymorphisms ( SNPs) have been identified in humans; however, the importance of most SNPs for health and disease is not understood. Most SNPs are indeed unimportant and because of often inadequately powered studies, many observations on SNP effects can not be repeated by other researchers. SNPs are at best shown to influence protein function or level, rarely to influence risk of disease, and almost never to influence total mortality, the ultimate endpoint. A well-known functional SNP in the tumor suppressor TP53 gene leads to increased longevity: in the Danish general population (n = 9219) homozygotes for the minor allele versus homozygotes for the major allele had an increase in median survival of 3 years. This is partly explained by increased survival after development of cancer or other diseases, in accordance with the observation that this Arg72Pro substitution in the p53 protein has important influence on cell death via increased apoptosis. Thus, the increased longevity may be due to a generally increased robustness after a diagnosis of any life-threatening disease. In contrast to widespread skepticism on the importance of SNPs in humans, this gain-of-function p53 SNP of importance for cell repair mechanisms has a profound influence on longevity Udgivelsesdato: 2008/1/15

M3 - Journal article

SN - 1538-4101

VL - 7

SP - 158

EP - 163

JO - Cell Cycle

JF - Cell Cycle

IS - 2

ER -