Association between MTHFR Gene Polymorphisms and the Risk of Autism Spectrum Disorders: A M eta‐Analysis
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 D ecember 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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In children from countries without folic acid supplementation, autism has been linked to two polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR), which is essential for DNA biosynthesis and the epigenetic process of DNA methylation.
“Similarly, in children from countries without folic acid supplementation, autism has been linked to two polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR), which is essential for DNA biosynthesis and the epigenetic process of DNA methylation (68).”
From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [68]
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- Authors
- Pu, D., Shen, Y., & Wu, J.
- Affiliations
- Jiangsu Province Hospital (CN)
- Boston Children's Hospital (US)
- Corresponding author
- Shen, Yiping
- Wu, Jie
- Venue
- Autism Research
- Publisher
- Wiley
- Published
- 2013-05-07
- Volume
- 6
- Issue
- 5
- Pages
- 384-392
- ISSN
- 1939-3792 (ISSN-L)
- 1939-3806
- OpenAlex
- W1952867757
- Cited by
- 130
- References
- 33
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 4 · 2023: 11 · 2022: 7 · 2021: 15 · 2020: 12 · 2019: 11 · 2018: 8 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 4
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Autism Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- MTHFR C677T polymorphism, MTHFR A1298C polymorphism, autism spectrum disorder, genetic susceptibility, folic acid fortification, periconceptional folic acid supplementation, DNA methylation, epigenetics, genetic association, congenital malformations, neurological disorders, cancer risk
- MeSH terms
- Child, Child Development Disorders, Pervasive, Cross-Cultural Comparison, Developing Countries, Folic Acid, Folic Acid Deficiency, Food, Fortified, Gene Frequency, Genotype, Genetic Carrier Screening, Humans, Polymorphism, Genetic, Risk Factors, Case-Control Studies, Genetic Predisposition to Disease, Methylenetetrahydrofolate Reductase (NADPH2), Epigenesis, Genetic
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