Abstract

BackgroundAutism spectrum disorder (ASD) is becoming increasingly prevalent of late. Methylenetetrahydrofolate reductase (MTHFR) has a significant role in folate metabolism. Owing to the inconsistencies and inconclusiveness on the association between MTHFR single nucleotide polymorphism (SNP) and ASD susceptibilities, a meta-analysis was conducted to settle the inconsistencies.MethodsFor this meta-analysis, a total of 15 manuscripts published up to January 26, 2020, were selected from PubMed, Google Scholar, Medline, WangFang, and CNKI databases using search terms “MTHFR” OR “methylenetetrahydrofolate reductase” AND “ASD” OR “Autism Spectrum Disorders” OR “Autism” AND “polymorphism” OR “susceptibility” OR “C677T” OR “A1298C”.ResultsThe findings of the meta-analysis indicated that MTHFR C677T polymorphism is remarkably associated with ASD in the five genetic models, viz., allelic, dominant, recessive, heterozygote, and homozygote. However, the MTHFR A1298C polymorphism was not found to be significantly related to ASD in the five genetic models. Subgroup analyses revealed significant associations of ASD with the MTHFR (C677T and A1298C) polymorphism. Sensitivity analysis showed that this meta-analysis was stable and reliable. No publication bias was identified in the associations between MTHFRC677T polymorphisms and ASD in the five genetic models, except for the one with regard to the associations between MTHFRA1298C polymorphisms and ASD in the five genetic models.ConclusionThis meta-analysis showed that MTHFR C677T polymorphism is a susceptibility factor for ASD, and MTHFR A1298C polymorphism is not associated with ASD susceptibility.

Highlights

  • Autism spectrum disorder (ASD) is becoming increasingly prevalent of late

  • The following criteria had to be satisfied by the studies to be incorporated in this meta-analysis: (1) Original studies on the correlation between Methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T/A1298C) and ASD; (2) Cohort or casecontrol designs; (3) All genotype frequency information is available; (4) Diagnostic criteria of ASD described in the Diagnostic and Statistical Manual of Mental Disorders

  • A total of 2609 cases and 7496 controls were enrolled from the 15 articles published on the correlation between MTHFR C677T polymorphism and ASD susceptibility

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Summary

Introduction

Autism spectrum disorder (ASD) is becoming increasingly prevalent of late. Methylenetetrahydrofolate reductase (MTHFR) has a significant role in folate metabolism. Owing to the inconsistencies and inconclusiveness on the association between MTHFR single nucleotide polymorphism (SNP) and ASD susceptibilities, a meta-analysis was conducted to settle the inconsistencies. Autism spectrum disorder (ASD) is one of the complex neurodevelopmental disorders, which has been increasingly recognized as a public health issue [1]. Folate/homocysteine (Hcy) levels act as a risk factor in ASD [14, 15], indicating the involvement of methylenetetrahydrofolate reductase (MTHFR) in ASD

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