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.
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