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

Tahereh Sadeghiyeh, Seyed Alireza Dastgheib, Khadijeh Mirzaee-Khoramabadi, Majid Morovati-Sharifabad, Mohammad Javad Akbarian-Bafghi, Zahra Poursharif, Seyed Reza Mirjalili, Hossein Neamatzadeh

Journal: Asian journal of psychiatry 2020;46():54-61

PMID: 31614268

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Child and Adolescent Psychiatric Research Center of Addiction and Behavioral Sciences, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.; Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.; Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: [email protected].; Department of Basic Science, Faculty of Veterinary Medicine, Ardakan University, Ardakan, Iran.; Department of Health Care Management, Bam University of Medical Sciences, Bam, Iran.; Department of Psychiatry, Tehran University of Medical Sciences, Tehran, Iran.; Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.; Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

DOI: 10.1016/j.ajp.2019.09.016

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MeSH Terms: Autism Spectrum Disorder, Genetic Predisposition to Disease, Humans, Methylenetetrahydrofolate Reductase (NADPH2)