TLR2 genetic diversity associated with the risk of Schizophrenia development in a Tunisian population

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Abstract Objectives: 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 of nine TLR2/TLR4 polymorphisms (TLR2: rs4696480T>A, rs3804099T>C, rs3804100T>C; TLR4: rs1927914G>A, rs10759932T>C, rs4986790A>G, rs4986791T>C, rs11536889G>C and rs11536891T>C) with susceptibility to SZ in a Tunisian population. Methods: TLR2-4 genotyping was done using a TaqMan 5’-nuclease assay for 150 SZ patients and 201 healthy controls (HC) with no history of psychiatric illness.Results: We found that only the TLR2 rs4696480T>A polymorphism was significantly associated with SZ. Indeed, the AA genotype was significantly associated with an increased risk of SZ (46% versus 31%, p= 4.7*10-3, OR =1.87 and 95% CI [1.18-2.97]). The frequency of the TA genotype was significantly more prevalent in HC than in SZ patients (27% versus 43%, p=2.1*10-3) and may be associated with protection against SZ (OR = 0.49 and 95% CI [0.30- 0.80]). The ACT haplotype of the TLR2 gene was identified as a risk haplotype for SZ. Moreover, we found a significant association between AA genotype and domestic violence (AA versus TT+AT; 71% versus 49%; p= 0.036, OR = 3.24, 95% CI = 1.20–10.80). Concerning the other polymorphisms no significant association was found.Conclusion: The results indicate that TLR2 genetic diversity may play a role in genetic vulnerability to SZ.

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