The association of inflammatory status and immunological parameters with single-nucleotide polymorphisms of cytokine and Toll-like receptor genes in patients with schizophrenia

Abstract

Schizophrenia is a multifactorial and clinically polymorphic disease with a significant hereditary component. The study of the influence of functionally significant polymorphisms of the genes regulating immune response and inflammation on the immune parameters in patients with schizophrenia is relevant for the development of new methods for predicting the course of the disease and finding new therapy targets. The aim of the study:To study the association of polymorphisms in cytokine and Toll-like receptor genes with the serum levels of immune mediators in patients with schizophrenia. Materials and methods: 95 patients diagnosed with schizophrenia and 99 healthy volunteers were recruited into the study. Polymorphisms of genes regulating the immune response (IL1B rs1143627, IL4 rs2243250, IL2 rs2069762, IL10 (rs1800896, rs1800872, rs1800871), IFNL rs8099917, IFNL rs12979860, TLR9 rs5743836, TLR9 rs352140, TLR3 rs3775291), the serum level of major cytokines and markers of systemic inflammation were determined. Results: The patients were found to have elevated levels of key pro-inflammatory cytokines IL-8 and IL-17A and other markers of systemic inflammation, as well as an increase in the content of antigen-antibody complexes in the bloodstream. Increased frequency of IL10 gene polymorphisms (rs1800896, rs1800872, rs1800871) was revealed in the patients with schizophrenia. A relationship between IL-6 and IL-8 levels and the carriage of IL1B T-511C (rs16944), IL10 1082A (rs1800896), IL10 592 C>A (rs1800872) and TLR3 Leu412Phe (G/A) (rs3775291) single nucleotide polymorphisms was found. Conclusion: The revealed associations may indicate a role of SNPs in cytokine and Toll-like receptor genes in modulating the network genetic interactions underlying certain immunological endophenotypes in the patients. Based on the results of this work and literature data, it is important to further study the relationship of immunogenetic markers in schizophrenia with the immune profiles of the disease and its clinical manifestations, including in larger samples of patients.

Pathways of Hypoxia-Inducible Factor (HIF) in the Orchestration of Uterine Fibroids Development

“…GWAS remains one of the most effective approaches to the search for “susceptibility” genes to human multifactorial diseases [ 69 , 70 , 71 , 72 ]. Using the GWAS catalog, we found that variations in 174 genes are associated with UF risk in different populations around the world (for instance, rs16991615 MCM8 , rs17631680 DNMT3AP1 , rs2306022 ITGA11 , rs2456181 ZNF346 , rs3820282 WNT4 , rs4335411 ZNF692 , rs5930554 AGKP2 , rs66998222 HNRNPA1P48 , rs78378222 TP53 , rs7986407 FOXO1 , rs8105767 ZNF257 , and rs9548898 COG6 ).…”