Background: Genetic variations in miRNAs and their binding sites may increase schizophrenia risk by disrupting miRNA-target interactions, impairing brain development, and elevating susceptibility to this disorder. This study employed in silico tools to predict the deleterious effects of single-nucleotide polymorphisms (SNPs) in overlapped miRNAs related to Th1/Th2 differentiation in schizophrenia, focusing on their impact on miRNA stability, structure, and target binding.

Methods: Overlapped miRNAs associated with Th1/Th2 differentiation in schizophrenia were retrieved from miRTarBase and miRWalk databases. To identify and predict the functional effects of SNPs located in the precursor and mature regions of candidate miRNAs, Ensembl, miRNASNP-v4, and SNP2TFBS databases were used. Finally, enrichment analysis of biological pathways was performed using NcPath database.

Findings: miRNASNP-v4 identified multiple SNPs across seven overlapped miRNAs (hsa-miR-107, hsa-miR-1827, hsa-miR-206, hsa-miR-320e, hsa-miR-4429, hsa-miR-4467, and hsa-miR-936), with the highest SNP counts in pre-miRNA and mature miRNA regions, particularly in hsa-miR-320e, hsa-miR-4467, and hsa-miR-936. SNPs rs1350983737 and rs1043872367 in hsa-miR-4467 exhibited the strongest and weakest influences on mature miRNA production, respectively. Notably, miR-4467 and miR-320e harbored the most seed region SNPs, potentially disrupting miRNA binding to 3′UTR of target mRNAs. Several SNPs were also found in miRNA promoter regions, potentially impairing transcription factor binding.

Conclusion: SNPs in miRNAs can affect both their expression and regulatory functions. Genetic variations in schizophrenia-related miRNAs represent important targets for further investigation to elucidate disease molecular mechanisms.