Association between MTHFR C677T polymorphism and neural tube defect risks: A comprehensive evaluation in three groups of NTD patients, mothers, and fathers

Birth Defects Res A Clin Mol Teratol. 2015 Jun;103(6):488-500. doi: 10.1002/bdra.23361. Epub 2015 Mar 24.


Background: The C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) gene has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results are inconclusive. In this study, we performed a meta-analysis in three groups to investigate the association between the MTHFR C677T polymorphism and NTD risk.

Methods: A computer retrieval of PubMed, Cochrane Library, CBM, and Embase for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analyzed with STATA (Version 13.0). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. A test for heterogeneity, a sensitivity analysis, and an assessment of publication bias were performed in our meta-analysis.

Results: Forty articles were included in this meta-analysis: 13 studies for Group A: 1329 NTD patients versus 2965 healthy controls; 34 studies for Group B: 3018 mothers with NTD progeny versus 8746 healthy controls; three studies for Group C: 157 fathers with NTD progeny versus 705 healthy controls. The analysis results show: allele contrast in NTD patients: OR = 1.445, 95% CI [1.186, 1.760]; allele contrast in mothers: OR = 1.342, 95% CI [1.166, 1.544]; allele contrast in fathers: OR = 1.062, 95% CI [0.821, 1.374].

Conclusion: We found no association between any of the fathers' genotypes and NTDs, whereas a significant correlation between MTHFR C677T polymorphism and NTD risk was found in NTD patients and in their mother.

Keywords: MTHFR C677T; NTDs; meta-analysis; neural tube defects; polymorphism.

Publication types

  • Meta-Analysis

MeSH terms

  • Fathers*
  • Genetic Association Studies
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Mothers*
  • Neural Tube Defects / epidemiology*
  • Neural Tube Defects / genetics*
  • Odds Ratio
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics*
  • PubMed
  • Risk Assessment


  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)