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 B12status) concentrations. The polymorphismstranscobalamin II (TCN2)c.776C>G,betaine-homocysteine S-methyltransferase (BHMT)c.742A>G,methylenetetrahydrofolate reductase (NAD(P)H) (MTHFR)c.677 C>T and theMTHFR677C-1298A-1317T haplotype modulate DS risk. The polymorphismsMTHFRc.677C>T and solute carrier family19 (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.