Cabello-Rangel Héctor, Sotelo-Ramírez Carlo Esteban, Jiménez-Pavon Joanna, Sanabrais-Jiménez Marco Antonio, Morales-Cedillo Pamela, Camarena Beatriz
Research Department, Hospital Psiquiatrico Fray Bernardino Alvarez, Ciudad de Mexico, Mexico.
Pharmacogenetics Department, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Ciudad de Mexico, Mexico.
BMC Psychiatry. 2025 Aug 22;25(1):806. doi: 10.1186/s12888-025-07270-9.
Clinical and genetic studies have suggested that immune dysregulation and neuroinflammation are involved in the pathogenesis of schizophrenia. Peripheral laboratory markers are accessible indicators linked to systemic inflammation and immune function. Genetic studies have demonstrated that blood parameters are highly heritable. Therefore, the aim of this study was to analyze the association between blood parameters and IL10, TNF, TLR2, and TLR6 gene polymorphisms in Mexican patients with schizophrenia.
We included 236 Mexican patients with schizophrenia. Peripheral blood samples were obtained in the early morning, prior the breakfast, from each participant. Complete blood count was analyzed. Genomic DNA was extracted, and genotyping was performed using TaqMan Discrimination assay of IL10 (rs1554286), TNF (rs1800629), TLR2 (rs7656411), and TLR6 (rs5743827). Association analyses between blood parameters and genotypes of the four genetic variants were performed using chi-square tests and ANOVA with Tukey's post-hoc multiple comparisons.
We observed higher monocyte levels (F = 5.57; p = 0.004) and monocyte-lymphocyte ratio (F = 5.49; p = 0.004) in patients carrying the GG genotype of rs7656411/TLR2 compared with TT or TG genotype carriers. Additionally, we observed a high frequency of the G allele of rs1800629/TNF, showing a low platelet count compared with carriers of the A allele (χ = 8.6, p = 0.003; OR = 3.82; CI, 1.46-9.96). Furthermore, we were unable to detect any gene-gene interaction in the analysis of MPV and platelet count after 1000-fold permutation testing.
Our findings indicate that blood parameter levels may be affected by genetic variants of TNF and TLR2 genes, indicating a potential role for innate immune response activation in schizophrenia in the Mexican population. Further studies with larger cohorts and comprehensive genetic analyses are essential to validate these findings and clarify the role of innate immune genes in schizophrenia.
临床和遗传学研究表明，免疫失调和神经炎症参与了精神分裂症的发病机制。外周实验室指标是与全身炎症和免疫功能相关的可获取指标。遗传学研究表明，血液参数具有高度遗传性。因此，本研究的目的是分析墨西哥精神分裂症患者血液参数与白细胞介素10（IL10）、肿瘤坏死因子（TNF）、Toll样受体2（TLR2）和Toll样受体6（TLR6）基因多态性之间的关联。
我们纳入了236名墨西哥精神分裂症患者。在早餐前的清晨采集每位参与者的外周血样本。分析全血细胞计数。提取基因组DNA，并使用TaqMan分型检测法对IL10（rs1554286）、TNF（rs1800629）、TLR2（rs7656411）和TLR6（rs5743827）进行基因分型。使用卡方检验和方差分析以及Tukey事后多重比较对血液参数与四种基因变异的基因型之间进行关联分析。
我们观察到，与携带rs7656411/TLR2基因TT或TG基因型的患者相比，携带GG基因型的患者单核细胞水平更高（F = 5.57；p = 0.004），单核细胞与淋巴细胞比值更高（F = 5.49；p = 0.004）。此外，我们观察到rs1800629/TNF基因G等位基因的频率较高，与携带A等位基因的患者相比，血小板计数较低（χ = 8.6，p = 0.003；OR = 3.82；CI，1.46 - 9.96）。此外，在进行1000次置换检验后，我们在分析平均血小板体积（MPV）和血小板计数时未检测到任何基因 - 基因相互作用。
我们的研究结果表明，血液参数水平可能受TNF和TLR2基因变异的影响，这表明在墨西哥人群中，先天性免疫反应激活在精神分裂症中可能发挥作用。进一步开展更大样本量的队列研究和全面的基因分析对于验证这些发现以及阐明先天性免疫基因在精神分裂症中的作用至关重要。
