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Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies

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  • Lifeng Yan
  • Lin Zhao
  • Yan Long
  • Peng Zou
  • Guixiang Ji
  • Aihua Gu
  • Peng Zhao

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.

Suggested Citation

  • Lifeng Yan & Lin Zhao & Yan Long & Peng Zou & Guixiang Ji & Aihua Gu & Peng Zhao, 2012. "Association of the Maternal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects in Offsprings: Evidence from 25 Case-Control Studies," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-8, October.
    • Handle: RePEc:plo:pone00:0041689
    DOI: 10.1371/journal.pone.0041689
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    Cited by:

    1. Jianxin Jiang & Yanfei Zhang & Liang Wei & Zhiyang Sun & Zhongmin Liu, 2014. "Association between MTHFD1 G1958A Polymorphism and Neural Tube Defects Susceptibility: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-9, June.
    2. Apolline Imbard & Jean-François Benoist & Henk J. Blom, 2013. "Neural Tube Defects, Folic Acid and Methylation," IJERPH, MDPI, vol. 10(9), pages 1-38, September.

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