Résumé :
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Background and study aim : Schizophrenia (SZ) is a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction plays a key etiopathogenic role. In order to explore the control of innate immune responses in SZ, we aimed to investigate the potential association between twelve TLR2, TLR4 and TLR9 variants (TLR2: rs4696480T > A, rs3804099T > C, rs3804100T > C; TLR4: rs1927914G > A, rs10759932T > C, rs4986790A > G, rs4986791T > C, rs11536889G > C, rs11536891T > C; TLR9: rs187084A > G, rs352139T > C and rs352140C > T) and SZ susceptibility in a Tunisian population. Patients and methods : This study included 150 patients and 201 healthy controls with no history of psychiatric illness. Genotyping was done using a TaqMan SNP genotyping assay. We also assessed a haplotype analysis for TLR2, TLR4 and TLR9 variants with SZ using Haploview 4.2 Software. Results : We found that the AA genotype of the TLR2 rs4696480T > A variant was significantly associated with an increased risk of SZ (46% vs. 31%, P = 4.7 × 10−3, OR = 1.87 and 95% CI [1.18–2.97]). The frequency of the TA genotype was significantly higher in the control group than in SZ patients (27% vs. 43%, P = 2.1 × 10−3) and may be associated with protection against SZ (OR = 0.49 and 95% CI [0.30–0.80]). Whereas, the TLR9 rs187084-GG genotype was higher in the control group compared to patients (16% vs. 5%, P = 1.6 × 10−3) and would present protection against SZ (OR = 0.28, CI = [0.10–0.68]). The ACT haplotype of the TLR2 and the ACC haplotype of the TLR9 gene were identified as a risk haplotypes for SZ (P = 0.04, OR = 9.30, 95% CI = [1.11–77.71]; P = 3 × 10−4, OR = 6.05, 95% CI = [2.29–15.98], respectively). Conclusion : The results indicate that TLR2 and TLR9 genetic diversity may play a role in genetic vulnerability to SZ. However, including more patients and evaluation of TLR2 and TLR9 expression are recommended. [Résumé d'auteur]
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