Aflouk Youssef, Kenz Amira, Saoud Hana, Yacoub Saloua, Zaafrane Ferid, Gaha Lotfi, Bel Hadj Jrad Besma
Laboratory of Genetics, Biodiversity, and Valorization of Bioresources GBVB (LR11ES41), Higher Institute of Biotechnology of Monastir (ISBM), University of Monastir, Monastir, Tunisia.
Regional Center of Blood Transfusion, University Hospital Farhat Hached, Sousse, Tunisia.
Biochem Genet. 2025 May 13. doi: 10.1007/s10528-025-11127-x.
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). 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) 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.
免疫调节异常被认为是精神分裂症（SCZ）的潜在机制之一。确实，由Toll样受体（TLR）复合物TLR2-1和TLR2-6触发的炎症改变在SCZ病理生理学和治疗反应方面受到了关注。然而，TLR1和TLR6的遗传贡献仍不清楚。因此，本研究旨在探讨TLR1和TLR6基因多态性与SCZ遗传易感性及治疗反应之间的可能关联。本研究纳入了240名对照者和226名患者，通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对TLR1和TLR6基因多态性进行基因分型。分析了与SCZ以及基于治疗反应的患者组之间的基因型、等位基因和单倍型关联。在显性模型中，与对照者相比，反应者中TLR1-S602I GG+TG和次要等位基因显著更高（p = 0.004；比值比[OR]=3.0，p = 0.002；OR分别为3.0）。治疗前，与TT携带者相比，携带TLR1-S602I GG+TG和TLR6-S249P TT+CT的男性患者显示出显著更高的精神科评定量表（SAPS）评分（p = 0.01）。在治疗反应方面，TLR1-S602I TT携带者的阴性症状评定量表（SANS）评分显著降低（p < 0.01）。此外，治疗后，GG+TG携带者的SANS评分显著低于TT携带者（p = 0.01）。此外，与治疗反应中TT+CT携带者（p = 0.6）相反，TLR6-S249P CC携带者的SANS评分显著降低（p < 0.01）。此外，在精神分裂症男性中，与TT相比，TLR1-S602I GG+TG显示发病年龄显著升高（p = 0.01）。总之，我们的研究结果表明，TLR1-S602I和TLR6-S249P可能是精神分裂症易感性和治疗反应预测的潜在遗传因素，尤其是在男性中。
