Toll-Like Receptor (TLR) 1, 2, and 6 Gene Polymorphisms Support Evidence of Innate Immune Factors in Schizophrenia

Introduction: Schizophrenia is a complex psychiatric disorder with an important genetic contribution. Immunological abnormalities have been reported in schizophrenia. Toll-like receptor (TLR) genes play an important role in the activation of the innate immune response, which may help to explain the presence of inflammation in people with this disorder. The aim of this study was to analyze the association of TLR1, TLR2, and TLR6 gene polymorphisms in the etiology of schizophrenia. Methods: We included 582 patients with schizophrenia and 525 healthy controls. Genetic analysis was performed using allelic discrimination with TaqMan probes. Results: We observed significant differences between patients and controls in the genotype and allele frequencies of TLR1/rs4833093 (chi 2 = 17.3, p = 0.0002; chi 2 = 15.9, p = 0.0001, respectively) and TLR2/rs5743709 (chi 2 = 29.5, p = 0.00001; chi 2 = 7.785, p = 0.0053, respectively), and in the allele frequencies of TLR6/rs3775073 (chi 2 = 31.1, p = 0.00001). Finally, we found an interaction between the TLR1/rs4833093 and TLR2/rs5743709 genes, which increased the risk of developing schizophrenia (OR = 2.29, 95% CI [1.75, 3.01]). Discussion: Our findings add to the evidence suggesting that the activation of innate immune response might play an important role in the development of schizophrenia.