Toll-like receptor 3 (TLR 3) polymorphisms predisposition to schizophrenia and bipolar disorder

Toll-like receptor 3 (TLR 3) abnormal inflammatory response was described as one of the possible mechanisms implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). However, the genetic predisposition of TLR 3 to these disorders' onset is still unclear. Therefore, the predisposition of TLR 3 functional variants L412F (rs3775291) and F459L (rs3775290) was examined in both disorders.

In a case-control study, 260 controls, 260 SCZ, and 130 BD patients were recruited and genotyped by PCR-RFLP. Genotypes, alleles, and haplotypes frequencies were compared between controls and patients based on clinical features. Statistical analyses were adjusted by gender and age and validated by Bonferroni correction. In the dominant model, our results showed significantly higher L412F AA + GA frequency in controls compared to BD patients (p_adjusted=0.004; OR_adjusted=0.5) and type I BD patients (p_adjusted=0.009; OR_adjusted=0.5). Moreover, BD BPRS scores were significantly lower in L412F AA + GA carriers compared to GG carriers (p = 0.001) before treatment. Otherwise, F459L TT + CT and minor allele frequencies were significantly elevated in the paranoid subgroup compared to controls (p = 0.004; OR = 2.1, p = 0.002; OR = 1.8, respectively). After antipsychotic treatment, SCZ SANS scores decreased significantly in F459L TT + CT and CC carriers (p < 10^- 4) and in TT + CT carriers compared to CC carriers (p = 0.001).

The present study suggests that L412F could be a protective genetic factor from BD onset. However, F459L could be a genetic risk factor for the paranoid subtype and a potential genetic predictor of SCZ negative symptoms treatment improvement.