Grant sponsor: A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
Association between MTHFR Gene Polymorphisms and the Risk of Autism Spectrum Disorders: A Meta-Analysis
Article first published online: 7 MAY 2013
© 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Volume 6, Issue 5, pages 384–392, October 2013
How to Cite
Pu, D., Shen, Y. and Wu, J. (2013), Association between MTHFR Gene Polymorphisms and the Risk of Autism Spectrum Disorders: A Meta-Analysis. Autism Res, 6: 384–392. doi: 10.1002/aur.1300
Declaration of Conflicting Interests: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
- Issue published online: 22 OCT 2013
- Article first published online: 7 MAY 2013
- Manuscript Accepted: 12 APR 2013
- Manuscript Received: 11 OCT 2012
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- methylenetetrahydrofolate reductase;
- autism spectrum disorders;
- folic acid;
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.