Affiliations: Unidade de Pesquisa em Genética e Biologia
Molecular (UPGEM), Faculdade de Medicina de São José do Rio Preto
(FAMERP), São José do Rio Preto, São Paulo, Brazil | Faculdade de Medicina de Ribeirão (USP),
Ribeirão Preto, São Paulo, Brazil | Fleury, Centro de Medicina Diagnóstica, São
Paulo, São Paulo, Brazil | Departamento de Epidemiologia e Saúde Coletiva da
Faculdade de Medicina de São José do Rio Preto (FAMERP), São
José do Rio Preto, São Paulo, Brazil
Note: [] Address for correspondence: Profa. Dra. Érika Cristina
Pavarino, UPGEM, FAMERP (Bloco U6), Av. Brigadeiro Faria Lima, n.° 5416,
São José do Rio Preto – SP, Brazil, CEP: 15.090-000. Tel.: +55 17 3201
5720; E-mail: erika@famerp.br
Abstract: Studies have shown that the maternal risk for Down syndrome (DS) may
be modulated by alterations in folate metabolism. The aim of this study was to
evaluate the influence of 12 genetic polymorphisms involved in folate
metabolism on maternal risk for DS. In addition, we evaluated the impact of
these polymorphisms on serum folate and plasma methylmalonic acid (MMA, an
indicator of vitamin B_{12} status) concentrations. The
polymorphisms transcobalamin II (TCN2) c.776C>G,
betaine-homocysteine S-methyltransferase (BHMT) c.742A>G,
methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR) c.677 C>T and
the MTHFR 677C-1298A-1317T haplotype modulate DS risk. The polymorphisms
MTHFR c.677C>T and solute carrier family 19 (folate transporter),
member 1 (SLC19A1) c.80 A>G modulate folate concentrations, whereas
the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR)
c.66A>G polymorphism affects the MMA concentration. These results are
consistent with the modulation of the maternal risk for DS by these
polymorphisms.
Keywords: Down syndrome, genetic polymorphism, folate metabolism
