Molecular and in silico analyses of SYN III gene variants in autism spectrum disorder

Abstract

Background: Defects in neurotransmission and synaptogenesis are noteworthy in the pathogenesis of ASD. Synapsin III (SYN III) is defined as a synaptic vesicle protein that plays an important role in synaptogenesis and regulation of neurotransmitter release and neurite outgrowth. Therefore, SYN III may associate with many neurodevelopmental diseases, including ASD. Aim: The aim of this study was to investigate whether the SYN III gene -631 C > G (rs133946) and -196 G > A (rs133945) polymorphisms are associated with susceptibility to ASD. Methods: SYN III variants and the risk of ASD were investigated in 26 healthy children and 24 ASD children. SYN III gene variants were genotyped by PCR–RFLP methods. The differences in genotype and allele frequencies between the ASD and control groups were calculated using the chi-square (χ2). We analysed the SYN III gene using web-based tools. Results: Our results suggest that the presence of the AA genotype of the SYN III -196 G > A (rs133945) polymorphism affects the characteristics and development of ASD in children (p = 0.012). SYN III -631 C > G (rs133946) polymorphism was not associated with ASD (p = 0.524). We have shown the prediction of gene–gene interaction that SYN III is co-expressed with 17 genes, physical interaction with 3 genes, and co-localization with 12 genes. The importance of different genes (SYN I, II, III, GABRD, NOS1AP, GNAO1) for ASD pathogenesis was revealed by GO analysis. Conclusion: Considering the role of SYN III and related genes, especially in the synaptic vesicle pathway and neurotransmission, its effect on ASD can be further investigated.