Winter temperature and UV are tightly linked to genetic changes in the p53 tumor suppressor pathway in Eastern Asia

Am J Hum Genet. 2009 Apr;84(4):534-41. doi: 10.1016/j.ajhg.2009.03.009. Epub 2009 Apr 2.

Abstract

The tumor suppressor p53 is a master sensor of stress. Two human-specific polymorphisms, p53 codon 72 and MDM2 SNP309, influence the activities of p53. There is a tight association between cold winter temperature and p53 Arg72 and between low UV intensity and MDM2 SNP309 G/G in a cohort of 4029 individuals across Eastern Asia that suggests causative selection. Moreover, the two polymorphisms are not coselected. Haplotype-based selection analysis further suggests that this is a striking example of two functional polymorphisms being strongly selected for in human populations in response to environmental stresses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian Continental Ancestry Group / genetics
  • Base Sequence
  • Cohort Studies
  • Cold Climate / adverse effects*
  • DNA Primers / genetics
  • Ethnic Groups / genetics
  • Far East
  • Gene Frequency
  • Genes, p53 / radiation effects*
  • Haplotypes
  • Humans
  • Leukemia Inhibitory Factor / genetics
  • Models, Genetic
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Seasons
  • Selection, Genetic
  • Stress, Physiological / radiation effects
  • Temperature
  • Transcriptional Activation
  • Ultraviolet Rays*

Substances

  • DNA Primers
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2