Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2012;7(10):e41689.
doi: 10.1371/journal.pone.0041689. Epub 2012 Oct 3.

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

Lifeng Yan  1 , Lin Zhao, Yan Long, Peng Zou, Guixiang Ji, Aihua Gu, Peng Zhao
Affiliations
Meta-Analysis

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

Lifeng Yan et al. PLoS One. 2012.

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The studies inclusion and exclusion procedures.
Figure 2
Figure 2. Forest plot of NTD risk associated with the maternal MTHFR C677T polymorphism (TT+CT vs. CC) in overall populations.
Figure 3
Figure 3. Begg's Funnel plot of NTD risk associated with the maternal MTHFR C677T polymorphism (TT vs. CC +CT) in overall populations.
Each point represents a separate study for the indicated association.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ (2001) Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood) 226: 243–270. - PubMed
    1. Koch MC, Stegmann K, Ziegler A, Schroter B, Ermert A (1998) Evaluation of the MTHFR C677T allele and the MTHFR gene locus in a German spina bifida population. Eur J Pediatr 157: 487–492. - PubMed
    1. Hosseini M, Houshmand M, Ebrahimi A (2011) MTHFR polymorphisms and breast cancer risk. Arch Med Sci 7: 134–137. - PMC - PubMed
    1. Zeisel SH (2009) Importance of methyl donors during reproduction. Am J Clin Nutr 89: 673S–677S. - PMC - PubMed
    1. Speer MC, Worley G, Mackey JF, Melvin E, Oakes WJ, et al. (1997) The thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) is not a major risk factor for neural tube defect in American Caucasians. The NTD Collaborative Group. Neurogenetics 1: 149–150. - PubMed

Publication types

Substances

Grants and funding

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.