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- W4387496600 abstract "Genome-wide association studies (GWAS) support a relationship between regulatory genes of the immune response and schizophrenia. Toll-like receptors (TLRs) are a main family of pattern recognition receptors involved in triggering the innate immune response. We identified association between the TLR1, TLR2 and TLR6 genes and the risk of developing schizophrenia. Therefore, the aim of the present study was evaluated the effect of the risk variants in TLR1, TLR2 and TLR6 in the gene expression levels and the amount of these proteins measured in peripheral blood mononuclear cells of patients with schizophrenia compared with a control group. We included 24 Mexican patients with schizophrenia from INPRFM, and 24 healthy controls. Positive selection of CD14+ cells with MACS® Technology was used to obtain monocytes. RNA was extracted from monocytes using TRIzolTM. cDNA was synthesized with SuperScriptTM IV VILOTM Master Mix. We analyzed the gene expression of TLR1, TLR2, TLR6 and ACTB as housekeeping gene with qRT-PCR with TaqMan probes. Protein was separated by SDS-PAGE and electro-transferred onto PVDF membrane. Expression of TLR1, TLR2 and TLR6 was analyzed by Western Blot with specific antibodies for each receptor. Immunoreactive bands were developed with Immobilon® Western reagent and detected with ChemiDoc MP Imaging System. The gene expression analysis showed that TLR1, TLR2 and TLR6 was downregulated in patients with schizophrenia, compared to controls (p=0.0009). The analysis of gene expression by alleles identified an under-expression of TLR1 in patient carriers of the G allele (p = 0.0001). Also, an increase in the expression of TLR2 (p = 0.0002) and TLR6 (p < 0.05) was observed in patient carriers of the variants of interest compared with the control subjects. Differences in protein expression of TLR6 was observed between patients (D.O.x mm2 =600) and controls (D.O.x mm2 =190). The present study replicated the findings reporting downregulation gene expression in patients with schizophrenia. Also, alterations in protein expression have been reported in patients with schizophrenia, compared with controls. Moreover, this is the first study that analyzed the impact of risk alleles of TLR genes and changes in the gene expression levels in Mexican patients with schizophrenia. Our preliminary findings could indicate that the gene expression levels are given by other factors and not for the risk alleles previously identified. Therefore, our findings suggest that TLR1, TLR2 and TLR6 play an important role in the pathophysiology of schizophrenia. However, these findings should be analyzed in a larger sample size and carry out functional studies to identify alterations in TLR genes supporting the role of innate immune response in schizophrenia." @default.
- W4387496600 created "2023-10-11" @default.
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- W4387496600 date "2023-10-01" @default.
- W4387496600 modified "2023-10-12" @default.
- W4387496600 title "W72. TOLL-LIKE RECEPTOR 1, 2 AND 6 GENE EXPRESSION IN MONOCYTES OF PATIENTS WITH SCHIZOPHRENIA" @default.
- W4387496600 doi "https://doi.org/10.1016/j.euroneuro.2023.08.259" @default.
- W4387496600 hasPublicationYear "2023" @default.
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