Association between MTHFR Gene Polymorphisms and the Risk of Autism Spectrum Disorders: A Meta-Analysis

Authors

  • Danhua Pu,

    1. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
    2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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  • Yiping Shen,

    Corresponding author
    1. Shanghai Children's Medical Center, Jiaotong University School of Medicine, Shanghai, China
    2. Departments of Laboratory Medicine and Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts
    • Address for correspondence and reprints: Jie Wu, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, China, 210029. E-mail: jie.wuyale@gmail.com. Yiping Shen (Co-correspondence author), Shanghai Children's Medical Center, Jiaotong University, Shanghai, China; Departments of Laboratory Medicine and Pathology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115. E-mail: Yiping.Shen@childrens.harvard.edu

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  • Jie Wu

    Corresponding author
    1. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
    2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
    • Address for correspondence and reprints: Jie Wu, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, China, 210029. E-mail: jie.wuyale@gmail.com. Yiping Shen (Co-correspondence author), Shanghai Children's Medical Center, Jiaotong University, Shanghai, China; Departments of Laboratory Medicine and Pathology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115. E-mail: Yiping.Shen@childrens.harvard.edu

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  • Grant sponsor: A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
  • Declaration of Conflicting Interests: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Abstract

Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta-analysis. Up to December 2012, eight case-control studies involving 1672 patients with ASD and 6760 controls were included for meta-analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.09–1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09–2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08–3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12–2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02–2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56–0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta-analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

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