Affiliations: Departamento de Genética, Universidade Federal
do Rio Grande do Sul, Porto Alegre, Brazil | Programa de Pós-Graduação em
Genética e Biologia Molecular, Universidade Federal do Rio Grande do
Sul, Porto Alegre, Brazil | Serviço de Genética Médica,
Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil | Instituto Nacional de Genética Médica Populacional – INAGEMP, Porto Alegre, Brazil
Note: [] Corresponding author: Lavínia Schuler-Faccini,
Departamento de Genética, Universidade Federal do Rio Grande do Sul,
Caixa Postal 15053, Agencia Campus UFRGS, CEP 91501-970/Porto Alegre RS,
Brazil. Tel.: +51 33086726; Fax: +51 33598010; E-mail:
lavinia.faccini@ufrgs.br
Abstract: The p53 family and its regulatory pathway play an important role as
regulators of developmental processes, limiting the propagation of aneuploid
cells. Its dysfunction or imbalance can lead to pathological abnormalities in
humans. The aim of this study was to evaluate the effect of maternal
polymorphisms TP53 c.215G>C (P72R), TP73 4 c.-30G>A and 14 c.-20C>T,
MDM2 c.14+309T>G (SNP309), MDM4 c.753+572C>T and USP7 c.2719-234G>A as
risk factors for Down Syndrome (DS) birth. A case-control study was conducted
with 263 mothers of DS children and 196 control mothers. The distribution of
these genotypic variants was similar between case and control mothers. However,
the combined alleles TP53 C and MDM2 G, and P53 C and USP7 A increased the risk
of having offspring with DS (OR=1.84 and 1.77; 95% CI; P < 0.007 and 0.018,
respectively). These results suggest that, although the individual
polymorphisms were not associated with DS birth, the effect of the combined
genotypes among TP53, MDM2 and USP7 genes indicates a possible role of TP53 and
its regulatory pathway as a risk factor for aneuploidy.
Keywords: Down syndrome, TP53, TP73, MDM2, MDM4, USP7
