Is the common 677C-->T mutation in the methylenetetrahydrofolate reductase gene a risk factor for neural tube defects? A meta-analysis

QJM. 1997 Feb;90(2):111-5. doi: 10.1093/qjmed/90.2.111.


The common 677C-->T mutation (+) in the 5,10-methylenetetrahydrofolate reductase gene, resulting in decreased activity of the enzyme, has been associated with spina bifida neural tube defects (NTD). We combined all known Dutch control groups, a total of 1273 individuals, and found a prevalence of the 677C-->T mutation of 8.4%. When compared with the frequencies in 55 SB patients and to mothers with a child with SB their parents, this gave an OR of 1.9 [95% CI 1.1-3.3] for mothers and an OR of 1.5 [95% CI 0.74-3.1] for patients. The frequency of this mutation and its associated risk for NTD may be population-dependent. However, the frequencies of the 677C-->T mutation in different national and international control groups are almost all in the same range. We therefore combined the observed frequencies of the 677C-->T mutation in all reported studies. The mutation was present in 9.2% of controls, resulting in ORs for all reported NTD patients and their parents of: 1.7 [95% CI: 1.1-2.6]; 1.8 [95% CI: 1.1-3.1] and 1.9 [95% CI: 1.3-2.8] for mothers (combined prevalence 14.5%), fathers (combined prevalence 15.5%) and NTD patients (combined prevalence 16.4%), respectively, vs. all international controls. This meta-analysis confirms that the 677C-->T mutation is a genetic risk factor for NTD.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Genetic Markers
  • Homozygote
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Mutation
  • Netherlands
  • Neural Tube Defects / genetics*
  • Odds Ratio
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Prevalence


  • Genetic Markers
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)