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Disease Markers
Volume 32 (2012), Issue 2, Pages 73-81

Maternal Risk for Down Syndrome Is Modulated by Genes Involved in Folate Metabolism

Bruna Lancia Zampieri,1 Joice Matos Biselli,1 Eny Maria Goloni-Bertollo,1 Hélio Vannucchi,2 Valdemir Melechco Carvalho,3 José Antônio Cordeiro,4 and Érika Cristina Pavarino1

1Unidade 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
2Faculdade de Medicina de Ribeirão (USP), Ribeirão Preto, São Paulo, Brazil
3Fleury, Centro de Medicina Diagnóstica, São Paulo, São Paulo, Brazil
4Departamento de Epidemiologia e Saúde Coletiva da Faculdade de Medicina de São José do Rio Preto (FAMERP), São José do Rio Preto, São Paulo, Brazil

Received 23 February 2012; Accepted 23 February 2012

Copyright © 2012 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 B12 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.