Role of folate metabolizing genes and homocysteine in mothers of Down syndrome children.

Objectives: Folates are essential nutrients required for the synthesis of DNA/RNA in cell division and segregation. Folates are reduced and methylated in the liver with the help of enzymes such as methylenetetrahydrofolate reductase (MTHFR), MTR MTRR, reduced folate carrier 1, and cystathionine-β-synthase. Variants in the genes encoding these enzymes may lead to hypomethylation, resulting in nondisjunction which in turn increases the risk for Down syndrome (DS). The present study was conducted to genotype these genes and to see their association with homocysteine levels.

Materials and methods: A total of 213 mothers having DS children and 220 mothers having normal children were enrolled in the study. Genomic DNA was isolated from lymphocytes followed by polymerase chain reaction/Restriction Fragment Length Polymorphism for genotyping. Homocysteine levels were checked by chemoassay utilizing coumarin-based fluorescent probe.

Results: Genotypic frequency of MTHFR 1298 A > C polymorphism was significantly different among cases and controls (χ ² = 5.83, P = 0.01), presence of C instead of A allele provided protection against DS in mothers (odds ratios = 0.57, 95% confidence interval = 0.35-0.91, P = 0.01). Higher levels of homocysteine were independently associated with the risk of having DS child (P = 0.0001).

Conclusion: Homocysteine acted as an independent risk factor in the present study and was not associated with folate metabolizing gene variants.