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Association between polymorphisms of TLR2-1-6 and bipolar disorder in a tunisian population

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Abstract

Background

Bipolar disorder (BD) is a complex neuropsychiatric disease that has been strongly linked to immune dysregulation. In particular, an abnormal inflammatory response mediated by toll-like receptor 2 − 1/6 (TLR2-1/6) was described in BD. Nevertheless, genetic factors’ contribution is still unknown. Thus, we suggested that functional polymorphisms of TLR2, 1 and 6 could be involved in BD predisposition.

Methods and results

TLR2, 1 and 6 polymorphisms were genotyped by PCR-RFLP in 292 controls and 131 patients from a Tunisian population. Polymorphisms and haplotype associations were explored in BD and binary logistic regression analysis was performed for more powerful associations. In dominant model, we found a significantly higher genotype and minor allele frequencies in healthy females compared to patients for TLR2-196-174Ins/Del (p = 0.04; OR = 0.3, p = 0.04; OR = 0.3, respectively) and for TLR6-S249P only with minor allele (p = 0.03; OR = 0.2). In contrast, TLR2-R677W CT + TT and T allele frequencies were significantly higher in BD (padjusted<10− 4; ORadjusted =46.6, p < 10− 4; OR = 6.3, respectively), specifically in females (CT + TT: 100%). Similarly, TLR1-R80T showed significantly increased GC + CC and C allele frequencies in patients compared to controls (padjusted=0.04; ORadjusted=4, p = 0.009; OR = 4.3, respectively). Moreover, haplotype investigation demonstrated that InsGTCGT (p < 10− 4, OR = 275) and delGCCGT (p = 0.03, OR = 18.5) were significantly overrepresented in BD patients compared to controls.

Conclusions

We suggest that TLR2-196-174Ins/Del and TLR6-S249P could be protective factors of females against BD. However, TLR2-R677W and TLR1-R80T could be strongly associated with higher risk of BD. Interestingly, TLR2-R677W could be a genetic marker for BD in females. However, further studies with larger groups are needed to confirm these findings.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon 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.

Funding

Our study 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, 5000, Tunisia

    Youssef Aflouk, Oumaima Inoubli, Amira Kenz & Besma Bel Hadj Jrad

  2. Regional Center of Blood Transfusion, University Hospital Farhat Hached, Sousse, Tunisia

    Saloua Yacoub

  3. Department of Psychiatry and Vulnerability to Psychoses Laboratory-CHU Fattouma Bourguiba Monastir, University of Monastir, Monastir, Tunisia

    Ferid Zaafrane & Lotfi Gaha

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  1. Youssef Aflouk
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  4. Saloua Yacoub
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Contributions

Besma Bel Hadj Jrad and Youssef Aflouk contributed to the design and conception of the study. Youssef Aflouk performed experiments in the laboratory and manuscript writing. All authors participated in data collection, analysis, and data interpretation. Besma Bel Hadj Jrad was responsible for manuscript correction and revision. All authors read and agreed on the final version of the manuscript.

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Correspondence to Youssef Aflouk.

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The ethical committee of research in life and health sciences of the Higher Institute of Biotechnology of Monastir, Tunisia approved this study, following Helsinki Declaration of 2013. Written informed consent was obtained from all subjects included in the study or from patients’ family member.

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Aflouk, Y., Inoubli, O., Kenz, A. et al. Association between polymorphisms of TLR2-1-6 and bipolar disorder in a tunisian population. Mol Biol Rep 50, 8877–8888 (2023). https://doi.org/10.1007/s11033-023-08758-x

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