Functional Variants of miR-143 Are Associated with Schizophrenia Susceptibility: A Preliminary Population-Based Study and Bioinformatics Analysis.

Single nucleotide polymorphisms within genes encoding microRNAs may alter the expression of microRNAs and their target genes, contributing to the etiology of psychiatric disorders. We aimed to investigate the link between rs4705342T/C and rs4705343T/C polymorphisms in the promoter region of miR-143 and the risk of schizophrenia (SCZ) in a sample of an Iranian population. In this experimental study, a total of 398 subjects were recruited. Genotyping carried out using allele-specific PCR (AS-PCR) method. Different bioinformatics databases and Cytoscape V3.4.0 software were used for the analysis of the gene-miRNA interaction network. The genotypic analysis of rs4705342C/T showed that CC genotype in the co-dominant model significantly decreased the risk of SCZ (p < 0.001). Also, a significantly reduced risk of SCZ was observed under allelic (p < 0.001), dominant (p = 0.007), and recessive (p = 0.001) models of this variant. As regards rs4705343T/C, significantly enhanced risk of SCZ was found under the co-dominant CC (p = 0.01) and recessive (p = 0.007) contrasted genetic models. For this variant, the C allele conferred an increased risk of SCZ by 1.41 fold. Haplotype analysis showed that the Crs4705342 Trs4705343 haplotype significantly diminished SCZ susceptibility. The result of the bioinformatics analysis showed that miR-143, as a critical miRNA, targets ERK5, ERBB3, HK2, and PKCε, the four major genes involved in SCZ development. Our findings suggest that these two polymorphisms might affect SCZ susceptibility. Elucidating the precise regulatory mechanisms of gene expression in the development of SCZ will help researchers discover a novel target for therapeutic interventions.