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Association between TLR2 polymorphisms (− 196–174 Ins/Del, R677W, R753Q, and P631H) and schizophrenia in a Tunisian population

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Abstract

Since immune dysregulation has been well studied in schizophrenia pathophysiology, recent studies showed a potent role of TLR2 in neuroinflammation process underlying schizophrenia pathogenesis. However, the genetic predisposition is still unclear. Thus, we hypothesized that TLR2 polymorphisms − 196–174 Ins/Del (rs111200466), R753Q (rs5743708), R677W (rs121917864), and P631H (rs5743704) could be involved in schizophrenia predisposition. A case–control study was performed on a Tunisian population composed of 250 healthy controls and 250 patients genotyped by PCR–RFLP. Genotype and allele distribution were evaluated with sex, schizophrenia subtypes, and other clinical features. We also assessed a haplotype analysis for TLR2 polymorphisms with schizophrenia. Our results showed higher ins/del genotype frequency in healthy women compared to patients (p = 0.006; OR = 0.2). In the other hand, logistic regression showed higher ins/del genotype frequency in controls compared to paranoid patients (p = 0.05; OR = 0.48, adjusted). Frequencies of CT and T allele of R677W were significantly higher in patients compared to controls (p < 10−4, OR = 10.39; p < 10−4, OR = 4, adjusted, respectively). R753Q polymorphism was exclusively detected in patients (GA + AA = 2.5%) particularly in men with disorganized subtype. P631H did not show any association with schizophrenia. Finally, haplotype analysis showed that InsGTC and delGTC were associated with higher risk of schizophrenia (p = 0.0001, OR = 8.58; p = 0.04, OR = 5.01, respectively). In the Tunisian population, our results suggested that TLR2 R677W could be associated with susceptibility for schizophrenia, while − 196–174 Ins/Del suggested a trend of protection in women. Otherwise, R753Q could have an effect on schizophrenia especially for disorganized subgroup.

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Acknowledgements

We are very grateful to the staff of Psychiatry and Hematology Department of CHU Fattouma Bourguiba of Monastir for providing us with samples and clinical information. We would like to thank Dr. YATOUJI Sonia (Faculty of Medicine, University of Monastir, Monastir, Tunisia) for providing us with AciI enzyme.

Funding

This work was supported by the Tunisian Ministry of Higher Education and Scientific Research, Tunisia.

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Authors and Affiliations

  1. Laboratory of Genetics, Biodiversity and Valorization of Bioresources GBVB (LR11ES41), Higher Institute of Biotechnology of Monastir (ISBM), University of Monastir, Monastir, Tunisia

    Youssef Aflouk, Oumaima Inoubli, Hana Saoud & Besma Bel Hadj Jrad

  2. Department of Psychiatry and Vulnerability to Psychoses Laboratory-CHU Monastir, University of Monastir, Monastir, Tunisia

    Ferid Zaafrane & Lotfi Gaha

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  1. Youssef Aflouk
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Correspondence to Youssef Aflouk.

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Aflouk, Y., Inoubli, O., Saoud, H. et al. Association between TLR2 polymorphisms (− 196–174 Ins/Del, R677W, R753Q, and P631H) and schizophrenia in a Tunisian population. Immunol Res 69, 541–552 (2021). https://doi.org/10.1007/s12026-021-09238-9

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