Analysis of polymorphisms in genes involved in folate metabolism and its impact on Down syndrome and other intellectual disability

- Distribution & risk association of MTR A2756G, MTHFD1 G1958A & CBS 844ins68 was analyzed in DS and other ID children.
- Gene-gene interaction and its association with risk of DS and other ID were also evaluated.
- Frequency of MTR 2756G allele, 2756AG & GG genotype were respectively 1.81, 1.68 and 3.86 fold higher in ID children as compared to control.
- The significant positive interactions observed for MTR & MTHFD1, MTR & CBS and MTHFD1 & CBS polymorphisms in ID children.
- Significant negative association was observed between MTR A2756G, MTHFD1G1958A & CBS 844ins68 for DS

Folate is one of the B vitamins and essential for cellular functioning because it donates one‑carbon for de novo purine and pyrimidine synthesis, required for DNA synthesis and repair. Deficiency or mutation in one of the cofactor or enzyme involved in folate/homocysteine metabolism may leads to DNA hypomethylation, abnormal DNA synthesis, DNA strand breakage, impaired DNA repair and neurological damages as well as abnormal chromosomal segregation and chromosomal breaks. MTR, MTHFD1 and CBS are the key enzymes involved in the folate/homocysteine metabolism. The present study analyzed the risk association of MTR A2756G, MTHFD1 G1958A and CBS 844ins68 in the Down syndrome and other intellectually disabled children from Gujarat, using PCR/PCR-RFLP technique. The results of the present study revealed the significant association between MTR A2756G polymorphism and risk for intellectual disability. The significant negative associations were observed among MTR A2756G or MTHFD1 G1958A polymorphisms and Down syndrome. The CBS ins +/ins + genotype showed 4.09 fold increased risk of intellectual disability.