Investigation of expression change of miR-135a-5p in autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that appears in early childhood (2-6 years). It is an important health problem affecting 1- 2% of the population in the world. While its prevalence was reported as 4.4/10000 30 years ago, the rapid increase in its incidence today necessitated more studies to understand the causes of ASD. Although genetic and environmental factors play a role in its etiology, the heritability gap observed in genetic studies points to the importance of epigenetic mechanisms. MicroRNAs (miRNAs), which are among the epigenetic mechanisms, affect physiological functions such as division, proliferation and differentiation in the cell by regulating post-transcriptional gene expression on mRNAs. In this thesis, it was aimed to investigate the possible role of miR-135a-5p in ASD, which we determined as a candidate with the bioinformatics analyzes we performed before. A total of 33 children, 16 with ASD and 17 with normal development, were included in the study. The level of miR-135a-5p in plasma samples was determined by qRT-PCR method. Our results showed that miR-135a-5p expression was decreased in the ASD group compared to the control group, although it did not reach the level of statistical significance. In terms of ASD severity, miR-135a-5p levels were found to be similar in mild+moderate and severe ASD groups. When the relationship between clinical features and miR-135a-5p expression level in the ASD group was analyzed, there was no correlation between miR-135a-5p expression levels and ABC total score, RBS-RTV total score, and CARS total score. A significant positive correlation was found between ABC Social Skills and Self-Care section and miR-135a-5p expression level. When the literature and bioinformatics analysis findings supporting the relationship of miR-135a-5p especially with cancer and the serotonergic system are evaluated together with our results obtained in this thesis study, it makes us think that miR-135a-5p is a molecule worthy of further studies as a candidate molecule in the etiology of ASD. It is necessary to carry out functional studies on the target transcripts of miR-135a-5p to confirm our results by increasing the number of subjects and to understand which pathway(s) play a role in this process. Keywords: autism spectrum disorder, epigenetics, microRNA, mir-135a-5p