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MTHFR C677T Polymorphism and Risk of Congenital Heart Defects: Evidence from 29 Case-Control and TDT Studies

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  • Wei Wang
  • Yujia Wang
  • Fangqi Gong
  • Weihua Zhu
  • Songling Fu

Abstract

Background: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme for folate metabolism in humans; it is encoded by the MTHFR gene. Several studies have assessed the association between MTHFR C677T polymorphism and the risk of congenital heart defects (CHDs), while the results were inconsistent. Methods and Findings: Multiple electronic databases were searched to identify relevant studies published up to July 22, 2012. Data from case-control and TDT studies were integrated in an allelic model using the Catmap and Metafor software. Twenty-nine publications were included in this meta-analysis. The overall meta-analysis showed significant association between MTHFR C677T polymorphism and CHDs risk in children with heterogeneity (Pheterogeneity = 0.000) and publication bias (Pegger = 0.039), but it turned into null after the trim-and-fill method was implemented (OR = 1.12, 95% CI = 0.95–1.31). Nevertheless, positive results were obtained after stratified by ethnicity and sample size in all subgroups except the mixed population. For mothers, there was significant association between the variant and CHDs without heterogeneity (Pheterogeneity = 0.150, OR = 1.16, 95% CI = 1.05–1.29) and publication bias (Pegger = 0.981). However, the results varied across each subgroup in the stratified analysis of ethnicity and sample size. Conclusions: Both infant and maternal MTHFR C677T polymorphisms may contribute to the risk of CHDs.

Suggested Citation

  • Wei Wang & Yujia Wang & Fangqi Gong & Weihua Zhu & Songling Fu, 2013. "MTHFR C677T Polymorphism and Risk of Congenital Heart Defects: Evidence from 29 Case-Control and TDT Studies," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-8, March.
    • Handle: RePEc:plo:pone00:0058041
    DOI: 10.1371/journal.pone.0058041
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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. Bo Zhu & Xiaomei Wu & Xueyuan Zhi & Lei Liu & Quanmei Zheng & Guifan Sun, 2014. "Methylenetetrahydrofolate Reductase C677T Polymorphism and Type 2 Diabetes Mellitus in Chinese Population: A Meta-Analysis of 29 Case-Control Studies," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-9, July.
    3. Hsiao-Ling Yang & Ya-Ling Yang & Chong Ho Yu & S. Pamela K. Shiao, 2018. "Meta-Prediction of MTHFR Gene Polymorphism and Air Pollution on the Risks of Congenital Heart Defects Worldwide: A Transgenerational Analysis," IJERPH, MDPI, vol. 15(8), pages 1-18, August.

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