Association between MTHFR gene polymorphism and susceptibility to autism spectrum disorders: Systematic review and meta-analysis

Objective: A growing number of studies have highlighted the potential link between MTHFR gene polymorphisms and autism spectrum disorder (ASD), however, the results are conflictive. Therefore, this meta-analysis was conducted to find a persuasive answer for possible association or lack of association between MTHFR gene polymorphism and ASD risk. Methods: Systematic search was conducted in PubMed, Web of Science, and Scopus considering the association between MTHFR gene (C677 T and A1298C) polymorphisms and the risk of ASD prior to Jun 2019. Results: A total of 17 studies for C677T and 8 studies for A1298C MTHFR gene polymorphism recognized eligible. The pooled results suggested a significant association between C677T SNP and ASD risk under dominant model (OR = 1.47, 95%CI = 1.13-2.93, REM), allelic model (OR = 1.37, 95% CI = 1.08-1.74, REM), and CT vs CC model (OR = 1.45, 95% CI = 1.13-1.85, REM). Moreover, the pooled results of subgroup analysis confirmed increased risk of ASD in Caucasians across all genetic models except recessive model. Besides, in spite of no significant association between A1298C SNP and ASD in overall population, subgroup analysis revealed that presence of A1298C SNP decrease risk of ASD in Caucasians. Conclusion: This meta-analysis suggested a significant association between MTHFR gene polymorphism (C677T and A1298C) and ASD risk.