Maternal MTHFR gene polymorphisms and the risk of Down syndrome offspring

Background: Methylenetetrahydrofolate reductase has been associated with Down’s syndrome. Aim: To study the frequency of methylenetetrahydrofolate reductase (MTHFR) 677C T mutation in Egyptian mothers having a child with Down syndrome (DS) and matched control mothers. Materials and methods: Eighty mothers, age < 40 years, with previous history of bearing a DS with karyotypically confirmed full trisomy 21 plus 30 healthy mothers with healthy children as matched control mothers. A case-control study to examine the association of genetic polymorphism in the MTHFR gene implicated in folate metabolism that known to let down the activity of this enzyme. Estimation of maternal plasma homocysteine (Hyc): methionine (Met) ratio and lymphocyte methotrexate (MTX) cytotoxicity to assess the occurrence of MTHFR 677C T mutation. Results: The MTHFR 677C T polymorphism is more prevalent among mothers of infant with DS compared with the controls, with an odd ratio of 1.9. In addition, mothers of infant with DS have significantly increased plasma levels as well as lymphocyte MTX cytotoxicity relative to the control. Conclusion: Aberrant folic acid metabolism secondary to MTHFR polymorphism leads to a significant reduction in plasma methionine and increasing the materials risk for having DS infant.