IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
TP53 AND MDM2: GENETIC VARIATION IN NATIVE AMERICANS
Autor/es:
JACOVAS, VC; BORTOLINI, MC; DE AZEVEDO, S; SALZANO, FM; RAMALLO V
Reunión:
Congreso; 59 Congresso Brasileiro de Genética; 2013
Resumen:
TP53 is a tumor suppressor gene and the corresponding protein p53, whose activity is regulated by post-transcriptional
systems, is a transcription factor, involved in many cellular functions (DNA repair, cell senescence, and apoptosis). Two
human-speci c polymorphisms a ect the p53 stress response pathway: p53 codon 72 (rs1042522, a C-G transversion
in exon 4 which leads to a Pro/Arg aminoacid change); and MDM2 SNP309 (rs2279744, a T-G transversion which
creates a binding site for the transcription factor SP1 MIM 189906). Allele frequencies are di erent ethnically and
geographically, supporting the hypothesis of selective pressure from environmental variables. e distribution would
be dependent on latitude, winter temperature or UV radiation. With the aim of better understanding the distribution
of these polymorphisms in America, we genotyped these two SNPs in 65 unrelated individuals from 4 Amerindian
populations (Aymara (N=17); Quechua (N=17); Guaraní-Ñandeva (N=15); and Guaraní-Kaiowa (N=16)). We also
included data from the literature, in a total of 415 samples and 15 Amerindian populations, and tested for correlations
with altitude and seven climate-related environmental variables (precipitation rates, minimum, maximum and mean
temperatures of warmest and coldest seasons). Pearson´s correlation coe cient and Spearman´s rho correlation
coe cient were computed to evaluate the relationship between SNP allele frequencies and each environmental variable.
For the P-values, two tailed tests were performed. Analysis was conducted with SPSS20.0. Hardy-Weinberg was tested
by the Web program (http://www.oege.org/software/hwe-mr-calc.shtml), and the statistical signi cance was assessed
by Fisher?s exact test. Both SNPs distributions were in HWE in all populations. For the p53-Arg allele, the most high
frequencies were reported in Brazilian Amerindian populations (especially high in Guaraní samples); while MDM2
309G showed high frequencies in Bolivian samples. Generally, there were no correlations between allele frequencies
and precipitation rates, but there is a trend for the MDM2 309G frequencies to increase with altitude (rho=0.711
p