title: Maternal risk for Down syndrome is modulated by genes involved in folate metabolism.
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<formula>_{12}</formula> 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.
authors.affiliation: Unidade de Pesquisa em Genética e Biologia Molecular (UPGEM), São José do Rio Preto, São Paulo, Brazil.
authors.forename: Bruna Lancia
authors.initials: BL
authors.lastname: Zampieri
authors.forename: Joice Matos
authors.initials: JM
authors.lastname: Biselli
authors.forename: Eny Maria
authors.initials: EM
authors.lastname: Goloni-Bertollo
authors.forename: Hélio
authors.initials: H
authors.lastname: Vannucchi
authors.forename: Valdemir Melechco
authors.initials: VM
authors.lastname: Carvalho
authors.forename: José Antônio
authors.initials: JA
authors.lastname: Cordeiro
authors.forename: Erika Cristina
authors.initials: EC
authors.lastname: Pavarino
mesh_terms: D000328:Adult; D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics; D053898:Biosynthetic Pathways / Q000235:genetics; D016022:Case-Control Studies; D004314:Down Syndrome / Q000209:etiology*; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000097:blood* / Q000378:metabolism; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008764:Methylmalonic Acid / Q000097:blood; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018566:Pregnancy, High-Risk / Q000235:genetics*; D058978:Reduced Folate Carrier Protein / Q000235:genetics; D012307:Risk Factors; D014155:Transcobalamins / Q000235:genetics
chemical_list: D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D014155:Transcobalamins; D008764:Methylmalonic Acid; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D050940:Betaine-Homocysteine S-Methyltransferase