Winter Temperature and UV Are Tightly Linked to Genetic Changes in the p53 Tumor Suppressor Pathway in Eastern Asia

• DOI: 10.1016/j.ajhg.2009.03.009
• Publication Date: 2009-04-03T08:31:12Z
• Authors: Hong Shi; Si-jie Tan; Hua Zhong; Wenwei Hu; Arnold Levine; Chun-jie Xiao; Yi Peng; Xue-bin Qi; Wei-hua Shou; Run-lin Z. Ma; Yi Li; Bing Su; Xin Lu
• Keywords: Cold stress

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.