Affiliations: Departamento de Genética, Universidade do Estado
do Rio de Janeiro, Rio de Janeiro, Brazil | Instituto de Nutrição, 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 Alcântara Gomes,
Departamento de Genética, Serviço de Genética Humana, Rua São
Francisco Xavier, 524, PHLC – sala 500, Maracanã 20550-013, Rio de
Janeiro, RJ, Brasil. Tel.: +55 21 2587 7107; Fax: +55 21 2587 7377; E-mail:
cbs@uerj.br
Abstract: Polymorphisms in genes encoding folate metabolizing enzymes have
been linked to an increased risk of maternal chromosomal nondisjunction in
several populations. With the purpose of evaluating this relationship, we
compared the frequencies of 677C>T and
1298A>C polymorphisms in the methylenetetrahydrofolate
reductase gene (MTHFR) and 66A>G in the methionine
synthase reductase gene (MTRR) between 103 young mothers of Down syndrome
(DS) individuals and 108 control mothers, whose offspring was karyotypically
normal, correlating it with an estimative of folate and – related
micronutrients levels intake. Maternal and paternal transmission frequencies of
MTHFR 677T allele were also examined to access potential parent-of-origin
effects. PCR-RFLP for genomic DNA was accomplished and allele/genotype
frequencies differences were determined using the x^{2}
test, whereas pattern of transmission of the MTHFR 677 allele was
analyzed by transmission disequilibrium test. None of the polymorphisms seemed
to be more frequent in case mothers than in controls, either individually or
combined. The estimative of nutritional intake revealed that folate consumption
median was inadequate in both groups, whereas methionine and zinc consumption
medians were significantly greater in control mothers. It suggests that such
interaction between genetic profile and environment could predispose this sub
group of women to have a DS child. Additional studies focusing the interaction
between nutritional intakes, biochemical data and folate pathway polymorphisms
are needed to confirm the present results. The possibility of neutralize the
biochemical negative effects of folate-related polymorphisms through oral
supplementation could provide new targets for DS prevention.
Keywords: Down syndrome, trisomy 21, folate, homocysteine, MTHFR
