miRNAs as biomarkers of autism spectrum disorder: a systematic review and meta-analysis

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex clinical manifestations that arise between 18 and 36 months of age. Social interaction defciencies, a restricted range of interests, and repetitive stereotyped behaviors are characteristics which are sometimes difcult to detect early. Several studies show that microRNAs (miRs/miRNAs) are strongly implicated in the development of the disorder and afect the expression of genes related to diferent neurological pathways involved in ASD. The present systematic review and meta-analysis addresses the current status of miRNA studies in diferent body fuids and the most frequently dysregulated miRNAs in patients with ASD. We used a combined approach to summarize miRNA fold changes in diferent studies using the mean values. In addition, we summarized p values for diferential miRNA expression using the Fisher method. Our literature search yielded a total of 133 relevant articles, 27 of which were selected for qualitative analysis based on the inclusion and exclusion criteria, and 16 studies evaluating miRNAs whose data were completely reported were ultimately included in the metaanalysis. The most frequently dysregulated miRNAs across the analyzed studies were miR-451a, miR-144-3p, miR-23b, miR-106b, miR150-5p, miR320a, miR92a-2-5p, and miR486-3p. Among the most dysregulated miRNAs in individuals with ASD, miR-451a is the most relevant to clinical practice and is associated with impaired social interaction. Other miRNAs, including miR19a-3p, miR-494, miR-142-3p, miR-3687, and miR-27a-3p, are diferentially expressed in various tissues and body fuids of patients with ASD. Therefore, all these miRNAs can be considered candidates for ASD biomarkers. Saliva may be the optimal biological fuid for miRNA measurements, because it is easy to collect from children compared to other biological fuids.