Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: evidence from 25 case-control studies

PLoS One. 2012;7(10):e41689. doi: 10.1371/journal.pone.0041689. Epub 2012 Oct 3.

Abstract

Background: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and is involved in DNA methylation, DNA synthesis, and DNA repair. In addition, it is a possible risk factor in neural tube defects (NTDs). The association of the C677T polymorphism in the MTHFR gene and NTD susceptibility has been widely demonstrated, but the results remain inconclusive. In this study, we performed a meta-analysis with 2429 cases and 3570 controls to investigate the effect of the MTHFR C677T polymorphism on NTDs.

Methods: An electronic search of PubMed and Embase database for papers on the MTHFR C677T polymorphism and NTD risk was performed. All data were analysed with STATA (version 11). Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were performed in our meta-analysis.

Results: A significant association between the MTHFR C677T polymorphism and NTD susceptibility was revealed in our meta-analysis ( TT versus CC: OR= 2.022, 95% CI: 1.508, 2.712; CT+TT versus CC: OR = 1.303, 95% CI: 1.089, 1.558; TT versus CC+CT: OR= 1.716, 95% CI: 1.448, 2.033; 2TT+CT versus 2CC+CT: OR= 1.330, 95% CI: 1.160, 1.525). Moreover, an increased NTD risk was found after stratification of the MTHFR C677T variant data by ethnicity and source of controls.

Conclusion: The results suggested the maternal MTHFR C677T polymorphism is a genetic risk factor for NTDs. Further functional studies to investigate folate-related gene polymorphisms, periconceptional multivitamin supplements, complex interactions, and the development of NTDs are warranted.

Publication types

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

MeSH terms

  • Case-Control Studies
  • Family Health
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Models, Genetic
  • Neural Tube Defects / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Risk Assessment / statistics & numerical data
  • Risk Factors

Substances

  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)

Grant support

This work is supported by the National Natural Science Foundation of China (Grant No. 81172694 and 30901210); Jiangsu Province's Natural Science Foundation (Proj. no. BK2009422); Doctoral Fund of Ministry of Education of China (Grant No. 20093234120001); and the Priority Academic Program Development of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.