Relevance of polymorphisms in TLR2/4 genes and their association with plasma cytokines for schizophrenia

Abstract

Schizophrenia is associated with altered levels of plasma cytokines. Toll-like receptors (TLRs) can be responsible for cytokine synthesis. It remains unclear whether genetic changes in TLRs, e.g. single-nucleotide polymorphisms (SNPs), account for altered levels. Here, we investigate the relationship between SNPs in TLR2 and TLR4 genes, cytokine levels, and cognition. This study included 281 participants (190 controls and 91 schizophrenia patients). Cognitive tasks using CANTAB and WAIS-III were administered to participants. Genotyping was performed using the Axiom-PMRA-R3 platform. Data were handled using Plink.V.1.9. We used ELISA to quantify plasma levels of cytokines (Interleukin-6 (IL-6), IL-8, IL-10, and Tumor necrosis factor (TNF-α)) and TLR activity as indicated by cytokine release from whole blood stimulated with TLR-2, -3, and -4 ligands. Linear regression of clumped SNPs revealed one TLR2 SNP [rs115751519] was associated with plasma IL-8 levels in patients. Four TLR4 SNPs [rs10983755, rs1927906, rs5030711 and rs57863323] were associated with plasma levels of IL-6 & TNF-α in patients. Three TLR4 SNPs [rs4986790, rs1554973 and rs5030711] were associated with IL-6 levels in controls. Finally, no significant associations were observed with cognition. Patients possessing a specific TLR2 or TLR4 genotype may be predisposed to elevated levels of cytokines but have no association with cognition.