Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis
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RESEARCH ARTICLE
Open Access
Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis Yan Li1, Shuang Qiu1, Jikang Shi1, Yanbo Guo1, Zhijun Li1, Yi Cheng2* and Yawen Liu1*
Abstract Background: 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. Methods: For 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”. Results: The 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 MTHF R 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. Conclusion: This meta-analysis showed that MTHFR C677T polymorphism is a susceptibility factor for ASD, and MTHFR A1298C polymorphism is not associated with ASD susceptibility. Keywords: Methylenetetrahydrofolate reductase, Autism spectrum disorder, Single nucleotide polymorphisms, Genetic models, Meta-analysis
Background Autism spectrum disorder (ASD) is one of the complex neurodevelopmental disorders, which has been increasingly recognized as a public health issue [1]. It affects 9‰ of the entire population of children, and the estimated ratio between male and female (M:F) children is * Correspondence: [email protected]; [email protected] 2 Institute of Translational Medicine, the First Hospital of Jilin University, Changchun 130021, China 1 Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
4:1 [2]. The prevalence rates of ASD in terms of percentages are approximately 1.52‰ in the Middle East [2–5], 14.7‰ in the USA [6, 7], 1.66‰ in China [8], and 6‰ in Australia [1, 9]. The distinguishing features of ASD include a set of behavioral phenotypes such as social communication deficits, restrictive and repetitive behaviors [10, 11], and worsened quality of life and family functioning for children with ASD and their parents [12]. Brain and nervous system dysfu
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