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Genetic Variants in the Folate Pathway and the Risk of Neural Tube Defects: A Meta-Analysis of the Published Literature

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Listed:
  • Ti Zhang
  • Jiao Lou
  • Rong Zhong
  • Jing Wu
  • Li Zou
  • Yu Sun
  • Xuzai Lu
  • Li Liu
  • Xiaoping Miao
  • Guanglian Xiong

Abstract

Background: Neural Tube Defects (NTDs) are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996–2011) and performed a comprehensive meta-analysis to provide empirical evidence on the association. Methods and Findings: We investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls), MTHFR A1298C (22 studies; 2602 cases, 4070 controls), MTR A2756G (9 studies; 843 cases, 1006 controls), MTRR A66G (8 studies; 703 cases, 1572 controls), and RFC-1 A80G (4 studies; 1107 cases, 1585 controls). We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07–1.42) and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24–1.92). However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models. Conclusions: Our meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs.

Suggested Citation

  • 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.
    • Handle: RePEc:plo:pone00:0059570
    DOI: 10.1371/journal.pone.0059570
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    References listed on IDEAS

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    1. David Moher & Alessandro Liberati & Jennifer Tetzlaff & Douglas G Altman & The PRISMA Group, 2009. "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-6, July.
    2. N/A, 2003. "Volume 8, Issue 4," Sociological Research Online, , vol. 8(4), pages 199-199, November.
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    Cited by:

    1. Hongtuan Zhang & Hui Ma & Liang Li & Zhihong Zhang & Yong Xu, 2013. "Association of Methylenetetrahydrofolate Dehydrogenase 1 Polymorphisms with Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-7, July.
    2. Bingxi Cai & Ti Zhang & Rong Zhong & Li Zou & Beibei Zhu & Wei Chen & Na Shen & Juntao Ke & Jiao Lou & Zhenling Wang & Yu Sun & Lifeng Liu & Ranran Song, 2014. "Genetic Variant in MTRR, but Not MTR, Is Associated with Risk of Congenital Heart Disease: An Integrated Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-7, March.
    3. 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.
    4. Vandana Rai & Upendra Yadav & Pradeep Kumar & Sushil Kumar Yadav & Om Prakesh Mishra, 2014. "Maternal Methylenetetrahydrofolate Reductase C677T Polymorphism and Down Syndrome Risk: A Meta-Analysis from 34 Studies," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-15, September.

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