Evidence of gene-gene interactions between MTHFD1 and MTHFR in relation to anterior encephalocele susceptibility in Northeast India

Anterior encephalocele (AE) is a rare congenital anomaly of the central nervous system which is thought to be associated with genetic defects in folate metabolism.This case-control study investigated the interactions of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1)-1958GA (rs2236225) and the methylenetetrahydrofolate reductase (MTHFR) - 677CT (rs1801133) and 1298AC (rs1801131) polymorphisms with the risk of AE in the Northeast Indian population. A total of 40 AE cases and 80 controls were investigated using polymerase chain reaction-restriction fragment length polymorphism technique.MTHFR 1298CC was significantly associated with AE risk (odds ratio [OR] 4.21; p = 0.01). The MTHFR haplotypes 677C-1298C/677T-1298A (OR, 2.50) and 677T-1298C (OR, 2.86) conferred risk in a progressive manner (χThe data support our hypothesis of gene-gene interaction between MTHFD1 and MTHFR and the risk of AE. Together with the MTHFR haplotypes, MTHFD1 elevates risk in a progressive manner. The minor allelic frequencies of the MTHFD1 1958GA and MTHFR 1298AC in our populations were similar to those reported from Southeast Asian population, suggesting a possible explanation for the prevalence of this malformation in these regions. Birth Defects Research 109:432-444, 2017. © 2017 Wiley Periodicals, Inc.