Affiliations: Departamento de Genética, Universidade do Estado
do Rio de Janeiro, Rio de Janeiro, Brazil
Note: [] Corresponding author: Dr. C.B. Santos-Rebouças,
Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto
Alcantara Gomes, Departamento de Genética, Rua São Francisco Xavier,
524, PHLC – sala 501, Maracanã 20550-013. Rio de Janeiro, RJ, Brazil.
Tel.: +55 21 2587 7107; Fax: +55 21 2587 7377; E-mail: cbs@uerj.br
Abstract: Recent evidence shows that almost 92% of the DS children are born from young mothers, suggesting
that other risk factors than advanced maternal age must be involved. In this
context, some studies demonstrated a possible link between DS and maternal
polymorphisms in genes involved in folate metabolism. These polymorphisms, as
well as low intake of folate could generate genomic instability, DNA
hypomethylation and abnormal segregation, leading to trisomy 21. We compared
the frequency of CBS 844ins68, MTR 2756A>G,
RFC-1 80G> A and TC 776C>G
polymorphisms among 114 case mothers and 110 matched controls, in order to
observe whether these variants act as risk factors for DS. The genotype
distributions revealed that there were not significant differences between both
samples. However, when we proceed the multiplicative interaction analyses
between the four polymorphisms described above together with the previously
studied MTHFR 677C>T, MTHFR
1298A>C and MTRR 66A>G
polymorphisms, our results show that the combined genotype TC 776CC /
MTHFR 677TT and TC 776CC / MTR 2756AG were significantly
higher in the control sample. Nevertheless, there was no significant
association after Bonferroni correction. Our results suggest that maternal
folate-related polymorphisms studied here have no influence on trisomy 21
susceptibility in subjects of Brazilian population.
Keywords: Down syndrome, folate, polymorphisms, TC
