Genetic Predisposition of TLR 1 and TLR 6 Polymorphisms to Schizophrenia Onset and Prediction of Treatment Response

Immunological dysregulation was described as one of the underlying mechanisms of schizophrenia (SCZ). Indeed, altered inflammation triggered by toll-like receptors (TLR) complexes TLR2-1 and TLR2-6 has gained attention in SCZ pathophysiology and treatment response. However, the genetic contribution of TLR1 and TLR6 remains unclear. Therefore, the present study aims to explore the possible association of TLR1 and TLR6 polymorphisms with the genetic predisposition to SCZ and treatment response. The current study included 240 controls and 226 patients genotyped for TLR1 and TLR6 polymorphisms by PCR-RFLP. Genotypic, allelic, and haplotype associations with SCZ and between patient groups based on their response to treatment were analyzed. In the dominant model, TLR1-S602I GG+TG and minor allele were significantly higher in responders compared to controls (p = 0.004; OR = 3.0, p = 0.002; OR = 3.0, respectively). Before treatment, male patients with TLR1-S602I GG+TG and TLR6-S249P TT+CT showed significantly higher SAPS scores (p = 0.01) compared to TT carriers. In response to treatment, TLR1-S602I TT carriers demonstrated a significant decrease in SANS scores (p < 10^-4). Moreover, SANS scores were significantly lower in GG+TG carriers compared to TT carriers (p = 0.01), after treatment. Furthermore, TLR6-S249P CC carriers showed a significant decrease in SANS scores (p < 10^-4) in opposite to TT+CT carriers (p = 0.6) in response to treatment. Moreover, TLR1-S602I GG+TG revealed a significantly elevated onset age compared to TT in schizophrenic males (p = 0.01). To conclude, our findings suggest that TLR1-S602I and TLR6-S249P could be potential genetic factors for schizophrenia susceptibility and the prediction of treatment response, particularly in males.