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Impact of antipsychotic treatment on methylation status of Interleukin-6 [IL-6] gene in Schizophrenia

机译:抗精神病药治疗对精神分裂症中白细胞介素-6 [IL-6]基因甲基化状态的影响

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Immunopathogenesis of schizophrenia has emerged as one of the predominant research paradigms in recent times. Based on the altered serum levels as well as gene expression, IL-6 has been considered as a peripheral biomarker of schizophrenia. However, the precise mechanism underlying the altered expression of IL6 in schizophrenia is inadequately known. Given the profound influence of environmental factors on schizophrenia risk, it is important to understand the effect of epigenetic changes on schizophrenia risk. Further, it is not known whether epigenetic changes modulate the expression of IL6 and its subsequent effects on the risk and progression of schizophrenia. In this study, we analysed and compared the methylation status of IL6 promoter sequence from ?1200bp to +27bp in antipsychotic-na?ve/free schizophrenia patients (N?=?47) and matched healthy controls (N?=?47) using bisulfite sequencing method. In addition, we also examined the methylation status in these patients at least after 3-months of treatment with antipsychotics (N?=?40). At baseline, a state of hypomethylation was observed in the IL6 promoter of schizophrenia subjects in comparison to healthy controls. This state of hypomethylation was shown to be reversed by the administration of antipsychotics. In summary, our observations emphasize a significant role for IL-6 promoter methylation in schizophrenia pathogenesis as well as treatment with antipsychotic medications.
机译:精神分裂症的免疫病理发生是最近的主要研究范式之一。基于改变的血清水平以及基因表达,IL-6被认为是精神分裂症的外周生物标志物。然而,依赖于精神分裂症中IL6改变表达的精确机制是不充分的。鉴于环境因素对精神分裂症风险的深刻影响,重要的是要了解表观遗传变化对精神分裂症风险的影响。此外,尚不清楚表观遗传变化是否调节IL6的表达及其随后对精神分裂症风险和进展的影响。在这项研究中,我们分析并将IL6启动子序列的甲基化状态与抗透视性 - Naαve /免费精神分裂症患者(n?= 47)和匹配的健康对照(n?= 47)进行了比较亚硫酸氢盐测序方法。此外,我们还至少在用抗精神病药治疗3个月后检查了这些患者的甲基化状态(n?= 40)。在基线上,与健康对照相比,在精神分裂症受试者的IL6启动子中观察到低甲基化状态。显示这种低甲基化的状态被抗精神病药施用逆转。总之,我们的观察结果强调了IL-6启动子甲基化在精神分症发病机制中的重要作用以及用抗精神病药治疗。

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