Transcobalamin and methionine synthase reductase mutated polymorphisms aggravate the risk of neural tube defects in humans

Neurosci Lett. 2003 Jul 3;344(3):189-92. doi: 10.1016/s0304-3940(03)00468-3.


The pathogenic mechanism of neural tube defects may involve genetic polymorphisms and nutritional factors related to homocysteine metabolism. We evaluated the association of polymorphisms of three genes affecting vitamin B12-dependent remethylation of homocysteine, transcobalamin (TC), methionine synthase (MTR) and MTR reductase (MTRR), combined or not with methylenetetrahydrofolate reductase (MTHFR), with the risk of having neural tube defect in 40 children with spina bifida and 58 matched controls from South Italy. MTR 2756 AG/GG, TC 777 CG/GG /MTHFR 677 CC and MTRR 66 GG /MTHFR 677 CC genotypes increased the risk with odds ratios of 2.6 (P=0.046), 2.4 (P=0.028) and 4.5 (P=0.023), respectively. In contrast, MTHFR 677 TT was protective (odds ratio=0.11, P=0.009). In conclusion, genetic determinants affecting the cellular availability or MTRR-dependent reduction of B12 may increase the risk of spina bifida.

MeSH terms

  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics*
  • Adolescent
  • Child
  • Child, Preschool
  • Female
  • Ferredoxin-NADP Reductase / genetics
  • Humans
  • Infant
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Mutation
  • Neural Tube Defects / genetics*
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Polymorphism, Genetic
  • Risk Factors
  • Transcobalamins / genetics*


  • Transcobalamins
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase