Association of MTHFR 677C>T and 1298A>C polymorphisms with susceptibility to autism: A systematic review and meta-analysis

• Published in: Asian journal of psychiatry 2019-12, Vol.46, p.54-61
• Main Authors: Sadeghiyeh, Tahereh, Dastgheib, Seyed Alireza, Mirzaee-Khoramabadi, Khadijeh, Morovati-Sharifabad, Majid, Akbarian-Bafghi, Mohammad Javad, Poursharif, Zahra, Mirjalili, Seyed Reza, Neamatzadeh, Hossein
• Format: Article
• Language: English
• Subjects: Autism; Autism Spectrum Disorder - ethnology; Autism Spectrum Disorder - genetics; Folate; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Humans; Meta-analysis; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; MTHFR Gene; Polymorphism
• ISSN: 1876-2018; 1876-2026
• DOI: 10.1016/j.ajp.2019.09.016

•The MTHFR 677C > T was significantly associated with risk of autism in overall and by ethnicity.•The MTHFR 1298A > C polymorphism was significantly associated with autism risk only in Caucasians.•The MTHFR polymorphisms have an ethnicity-specific effect in autism susceptibility.•The MTHFR polymorphisms could be used as a diagnostic marker of autism by ethnicity background. Several studies have investigated association of MTHFR 677C > T and 1298A > C polymorphisms with risk of autism, but they have reported controversial and inconclusive results. The present meta-analysis was designed to evaluate association of MTHFR 677C > T and 1298A > C polymorphisms with risk of autism. A comprehensive literature search was done in PubMed, EMBASE, and CNKI databases to identify all eligible publications up to April 01, 2019. Finally, 25 case-control studies including 18 studies on MTHFR 677C > T and 7 studies on MTHFR 1298A > C polymorphism were selected. Overall, a significant association was found between MTHFR 677C > T and an increased risk of autism under all five genetic models (T vs. C: OR = 1.483, 95% CI 1.188–1.850, p ≤ 0.001; TT vs. CC: OR = 1.834, 95% CI 1.155–2.913, p = 0.010; TC vs. CC: OR = 1.512, 95% CI 1.101–2.078, p = 0.011; TT + TC vs. CC: OR = 1.632, 95% CI 1.261–2.113, p ≤ 0.001; and TT vs. TC + CC: OR = 1.427, 95% CI 1.002–2.032, p = 0.049). However, no significant association was found between MTHFR 1298A > C and autism risk. Stratified analyses showed that MTHFR 677C > T and 1298A > C polymorphisms are involved in genetic susceptibility of autism by ethnicity. Results of this meta-analysis indicated that MTHFR 677C > T polymorphism may be associated with increased risk of autism in overall and by ethnicity, while MTHFR 1298A > C was reported to be significantly associated with the risk of autism only in Caucasians. MTHFR polymorphisms could be used as a diagnostic marker for autism with respect to ethnicity background.