Functional Genomics of Vitamin B12 Metabolism Genes and Neural Tube Defect Risk in North East Nigeria

Neural tube defects (NTDs) are among the most common congenital anomalies worldwide, with folate and vitamin B12 metabolism gene variants recognised as significant genetic risk factors. In North East Nigeria, NTD rates appear elevated in hospital-based reports, yet the genetic contribution through folate and B12 pathway genes has not been studied. This study investigated functional genetic variants in vitamin B12 metabolism genes (MTHFR, MTR, MTRR, and TCN2) and their association with NTD risk in North East Nigeria. A case-control study enrolled 90 mothers of NTD-affected children and 90 mothers of unaffected children at the Federal Medical Centre Nguru, Yobe State, and the University of Maiduguri Teaching Hospital, Borno State. Genotyping of MTHFR C677T, MTHFR A1298C, MTR A2756G, MTRR A66G, and TCN2 C776G polymorphisms was performed by PCR-RFLP. Plasma homocysteine and serum vitamin B12 levels were measured biochemically. The MTHFR 677TT genotype was significantly more prevalent among case mothers, particularly in the context of low dietary B12 intake. Gene-nutrient interaction was a significant predictor of NTD risk. Periconceptional B12 supplementation is recommended based on these genetic risk data. Keywords: neural tube defects, MTHFR, vitamin B12, North East Nigeria, gene-nutrient interaction