5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects

Am J Med Genet. 1996 Jun 28;63(4):610-4. doi: 10.1002/(SICI)1096-8628(19960628)63:4<610::AID-AJMG15>3.0.CO;2-L.


Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C-->T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C-->T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C-->T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD.

Publication types

  • Comparative Study

MeSH terms

  • 5,10-Methylenetetrahydrofolate Reductase (FADH2)
  • Adult
  • Alleles
  • Anencephaly / enzymology
  • Anencephaly / genetics
  • Black or African American
  • Enzyme Stability
  • Female
  • Fetus / abnormalities
  • Fetus / cytology
  • Fetus / pathology
  • Homozygote
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Molecular Sequence Data
  • Neural Tube Defects / enzymology*
  • Neural Tube Defects / genetics*
  • Oxidoreductases / genetics*
  • Polymorphism, Genetic*
  • Risk Factors
  • Spinal Dysraphism / enzymology
  • Spinal Dysraphism / genetics
  • White People / genetics


  • Oxidoreductases
  • 5,10-Methylenetetrahydrofolate Reductase (FADH2)
  • Methylenetetrahydrofolate Reductase (NADPH2)

Associated data

  • GENBANK/U09806