Abstract
Background:Schizophrenia is a severe psychiatric disorder with a heterogeneous clinical phenotype. The association of interleukins and other cytokines and their receptors with schizophrenia has been previously reported. Additionally, a number of studies have reported altered mico-RNA (miRNA) expression in schizophrenia and other psychiatric disorders. The aim of our study was to explore the possible association of miR-31, miR-146a, miR-181c and miR-155 with schizophrenia pathogenesis, as well as their link toIL2gene expression in disease.Methods: For this case-control study, 225 patients with paranoid schizophrenia and 225 sex- and age-matched controls with no family history of schizophrenia were recruited. The expression of studied miRNAs and theIL2gene was measured using qPCR. DNA samples of all patients and controls were genotyped forIL2rs2069778 single nucleotide polymorphism (SNP) using PCR with sequence specific primers (PCR-SSP). Statistical analyses include the Mann-Whitney U-test and Fischer’s exact test.Results: All studied miRNAs were over-expressed in schizophrenic patientsIL2gene expression was down-regulated in schizophrenic patients. TheIL2rs2069778 SNP is not associated with schizophrenia but regulates expression of theIL2 gene.Conclusions: Over-expression of studied miRNAs and down-regulation ofIL2gene expression may be considered as genetic risk factors for chronic schizophrenia. Abnormalities in studied miRNA expressions result in the deregulation of the T-cell receptor signaling pathway in schizophrenia.
Highlights
Schizophrenia (OMIM code: 181500) is a severe psychiatric disorder with a heterogeneous clinical phenotype1
We studied the possible association of the IL2 rs2069778 single nucleotide polymorphism (SNP) genotype with IL2 and miRNA levels
We studied mRNA expression levels of the IL2 gene in schizophrenia and its possible association with the IL2 rs2069778 C/T SNP
Summary
Schizophrenia (OMIM code: 181500) is a severe psychiatric disorder with a heterogeneous clinical phenotype. While the etiology of this disorder remains largely unknown, it has become evident that immune-inflammatory processes play an important multilevel role in disease development and progression. Cytokines and chemokines are essential signal mediators of the immune system that modulate and guide immune/inflammatory responses as well as perform a wide range of other functions related to cell survival, proliferation, differentiation and migration. Cytokines and chemokines are essential signal mediators of the immune system that modulate and guide immune/inflammatory responses as well as perform a wide range of other functions related to cell survival, proliferation, differentiation and migration5 Considering their biological importance, cytokines, especially interleukins (IL), have received considerable attention in the context of schizophrenia. Abnormalities in studied miRNA expressions result in the deregulation of the T-cell receptor signaling
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