Folate gene polymorphisms and the risk of down syndrome pregnancies in young Italian women

Maternal impairments in folate metabolism and elevated homocysteinemia are known risk factors for having a child with Down syndrome (DS) at a young age. The 80G > A polymorphism of the reduced folate carrier gene (RFC-1) has been recently demonstrate(l to affect plasma folate and homocysteine levels, alone or in combination with the 677C > T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. We performed the I)resent study on 80 Italian mothers of I)S individuals, aged less than 35 at conception, and I I I Italian control mothers, to study the role of the RFC-1 80G > A, MTHFR 677C > T, and MTHFR 1298A > C genotypes to the risk of,I DS offspring at a young maternal age. When polymorphisms were considered alone, both allele and genotype frequencies did not significantly differ between DS mothers and control mothers. However, the combined MTHFR677TT/RFC-1 80GG genotype was borderline associated with an increased risk (OR 6 (Cl 95% 1 -035-9), P=0.05), and to be MTHF1298AA/RFC-1 80(GA or AA) was inversely associated with the risk (OR 0.36 (Cl 95%: 0.14-0.96), P=0.04). Present results seem to indicate that none of the RFC-1 80G > A, MTHFR 677C > T and MTHFR 1298A > C polymorphisms is an independent risk Factor fora DS offspring at a young maternal age; however, a role for the combined MTHFR/RFC-1 genotypes in the risk of DS I)regnancies among young Italian women cannot be excluded. (c) 2006 Wiley-Liss, Inc.