The correlation between environmental variables and variations in genes of the p53 network

JACOVAS, VC; BORTOLINI MC; SALZANO FM; RAMALLO V

Congreso; 60º CONGRESSO BRASILEIRO DE GENÉTICA; 2014

Tumor suppressor p53 is a transcriptional factor (encoded by gene TP53), that maintain genomic integrity in response to various stress stimuli such as DNA damage and hypoxia. In normal unstressed cells, p53 is a very unstable protein with a very short half-life and its principal cellular antagonist is the MDM2 protein. It is well known that two human-specific single nucleotide polymorphisms (SNPs) affect the p53 stress response pathway: TP53 codon 72 rs1042522; Pro>Arg, and MDM2 SNP309 (rs2279744; a T>G mutation that creates a binding site for the SP1 MIM 189906 transcription factor). Allele frequencies for these SNPs are strikingly different among human populations, supporting the hypothesis of a selective pressure from environmental variables, such as latitude, temperature and/or UV radiation. The present study aims to better understand the distribution of these polymorphisms in Amerindians and populations with high Amerindian ancestry (N=. 284): Aymara (n=17); Quechua (n=17); Guaraní Ñandeva (n=15); Guaraní Kaiowa (n=16); Uros (n=22); Anapia (n=17); Amantani (n=31); Taquile (n=43); Andoas (n=61); Yanke (n=10); Chivay (n=18); and Cabanaconde (n=17). Data from the literature were also included in the analysis (88 samples those four Amerindian populations). Pearson´s correlation coefficient and Spearman´s rho correlation coefficient tests evaluated the relationship between the SNP allele frequencies and each environmental variable (annual precipitation mean, minimum and annual mean temperature and maximum temperature of the warmest month). All statistical tests were two-sided and p