Gene polymorphisms of miR-323b and miR-1343 that regulate kininogen L are associated with schizophrenia susceptibility: A preliminary population‑based study

TL;DR

This study found that certain gene variations in miR-323b and miR-1343 are linked to schizophrenia risk and specific symptoms like auditory hallucinations.

Contribution

The study identifies novel miRNA-related SNPs associated with schizophrenia susceptibility and symptom manifestation.

Findings

The hsa-miR-323b-rs56103835 mutation is significantly linked to schizophrenia under a dominant model.

The hsa-miR-1343-rs2986407 mutation increases the risk of auditory hallucinations in schizophrenia patients.

A three-factor model involving miR-SNPs showed potential but not significant interaction with schizophrenia.

Abstract

miRNA-related single-nucleotide polymorphism (miR-SNP) is a type of functional SNP that affects the regulatory functions of miRNA genes, miRNA binding sites, or components of miRNA biogenesis. This study aimed to explore the relationship between miRNA gene polymorphisms that regulate the kininogen L protein and schizophrenia (SCZ). Bioinformatics methods predicted miRNA gene polymorphism sites regulating the kininogen L protein. The polymorphisms of rs56103835, rs6513496, rs651349, and rs2986407 were detected using improved multiple ligase detection reaction multiple SNP typing technologies in 513 SCZ patients and 509 controls. The association of miR-SNP variations with SCZ susceptibility and symptoms was evaluated using SNPstat to determine the optimal inheritance model. Generalized multifactor dimensionality reduction analysis and logistic regression were used to calculate miR-SNP interactions. The association between hsa-miR-323b-rs56103835 and SCZ was statistically significant under the dominant model. The result of gene–gene interaction showed that the three-factor model (rs56103835/rs2986407/rs2155248) was the best, but it could not be considered significantly related to SCZ. Additionally, SCZ patients with the CC or CT genotype on rs2986407 were more likely to experience auditory hallucinations than those with the TT genotype. Our data revealed that the mutation of hsa-miR-323b-rs56103835 from C to T was associated with susceptibility to SCZ. The mutation of hsa-miR-1343-rs2986407 from T to C increases the risk of auditory hallucinations in SCZ patients.

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