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Association between MTHFD1 G1958A Polymorphism and Neural Tube Defects Susceptibility: A Meta-Analysis

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  • Jianxin Jiang
  • Yanfei Zhang
  • Liang Wei
  • Zhiyang Sun
  • Zhongmin Liu

Abstract

Objectives: The methylenetetrahydrofolate dehydrogenase (MTHFD1) gene, as one of the key genes involved in the folate pathway, has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs). However, the results of published studies are contradictory and inconclusive. Thus, this meta-analysis aimed to evaluate the effect of the common polymorphism in the MTHFD1 gene, the G1958A (R653Q, dbSNP ID: rs2236225) variant, on the risk of NTDs in all eligible studies. Methods: Relevant literature published before January 3, 2014 was retrieved from the MEDLINE, EMBASE, Cochrane Library, and CBM databases. Pooled crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the MTHFD1 G1958A polymorphism and NTDs risk. Results: We performed a meta-analysis of nine studies with a total of 4,302 NTDs patients and 4,238 healthy controls. Our results demonstrated a significant correlation between the MTHFD1 G1958A polymorphism and NTDs in an overall meta-analysis. For family-based studies, the study subjects were classified as NTD cases, mothers with NTDs offspring, and fathers with NTDs offspring. We found no association between any of the fathers’ genotypes and NTDs, whereas there was a clear excess of the 1958A allele in the mothers of children with NTDs compared with controls individuals. Conclusions: In summary, our meta-analysis strongly suggests that the MTHFD1 G1958A polymorphism might be associated with maternal risk for NTDs in Caucasian populations. However, the evidence of this association should be interpreted with caution due to the selective nature of publication of genetic association studies.

Suggested Citation

  • 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.
  • Handle: RePEc:plo:pone00:0101169
    DOI: 10.1371/journal.pone.0101169
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    References listed on IDEAS

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    1. 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.
    2. Ti Zhang & Jiao Lou & Rong Zhong & Jing Wu & Li Zou & Yu Sun & Xuzai Lu & Li Liu & Xiaoping Miao & Guanglian Xiong, 2013. "Genetic Variants in the Folate Pathway and the Risk of Neural Tube Defects: A Meta-Analysis of the Published Literature," PLOS ONE, Public Library of Science, vol. 8(4), pages 1-10, April.
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