Abstract
Immune dysregulation has been widely described in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). Particularly, TLR4-altered activation was proposed as one of the underlying processes of psychosis onset. Since TLR4 activation was altered by T399I and D299G polymorphisms, we hypothesized that those variants could present common genetic factors of SCZ and BD. A total of 293 healthy volunteers and 335 psychotic patients were genotyped using PCR–RFLP. Genotype, allele, and haplotype distribution between controls and patients were evaluated according to clinical parameters. Statistical analyses were adjusted by logistic regression. In dominant model, T399I CT + TT and allele frequency were significantly higher in controls compared to psychotic population (p = 0.004, p = 0.002, respectively), SCZ (p = 0.02, p = 0.01, respectively), and BD (p = 0.03, p = 0.02, respectively). Similarly, D299G AG + GG and allele frequency were significantly higher in controls compared to psychotic population (p = 0.04, p = 0.04, respectively) and SCZ (p = 0.04, p = 0.03, respectively). T399I CT + TT and T allele were overrepresented in controls compared to paranoid subgroup (Padjusted = 0.04, p = 0.04, respectively) and type I BD (p = 0.04). Moreover, T399I and D299G were less prevalent in SCZ late-onset age (p = 0.03, p = 0.02, respectively). TA haplotype was associated with protection from psychoses (p = 0.02) and particularly from schizophrenia (p = 0.04). In conclusion, TLR4 polymorphisms could present a preventive genetic background against psychoses onset in a Tunisian population. While T399I could be associated with protection against SCZ and BD, presenting an overlapping genetic factor between those psychoses, D299G was suggested to be associated with protection only from schizophrenia.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We are deeply thankful to all members of the Psychiatry Department of CHU Fattouma Bourguiba of Monastir and the Regional Center of Blood Transfusion of the same hospital and of CHU Farhat Hached of Sousse for providing us with samples and clinical information of all subjects.
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Our study was supported by the Tunisian Ministry of Higher Education and Scientific Research, Tunisia.
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BBHJ and YA contributed to the design and conception of the study. YA performed experiments in the laboratory and manuscript writing. HS participated in samples collection and data interpretation. Oumaima Inoubli performed statistical analysis. All authors participated in data collection, analysis, and data interpretation. BBHJ was responsible for manuscript correction and revision. All authors read and agreed on the final version of the manuscript.
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Aflouk, Y., Saoud, H., Inoubli, O. et al. TLR4 Polymorphisms (T399I/D299G) Association with Schizophrenia and Bipolar Disorder in a Tunisian Population. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10553-z
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DOI: https://doi.org/10.1007/s10528-023-10553-z