Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
J Psychiatr Res. 2011 Nov;45(11):1439-44. doi: 10.1016/j.jpsychires.2011.06.003. Epub 2011 Jun 22.
Recent studies indicate a role of excessive interleukin-6 (IL-6) signaling in the pathogenesis of schizophrenia. A previous study reported a significant association of schizophrenia with the IL-6 receptor (IL-6R) gene Asp358Ala polymorphism, which is known to regulate circulating IL-6 and soluble IL-6R (sIL-6R) levels in healthy subjects. To further examine the influence of the polymorphism in schizophrenic patients, we compared the plasma levels of IL-6 and sIL-6R between schizophrenic patients and healthy controls for each genotype of the Asp358Ala polymorphism. Asp358Ala genotyping and plasma IL-6 level measurements were performed in 104 patients with schizophrenia and 112 healthy controls. Of these participants, 53 schizophrenic patients and 49 controls were selected for the measurement of plasma sIL-6R levels. A two-way factorial analysis of covariance was performed with the transformed plasma levels as the dependent variable, diagnosis and genotype as independent variables, and sex and age as covariates. No significant diagnosis × genotype interaction was observed for IL-6 and sIL-6R levels. The Ala allele of Asp358Ala was significantly associated with higher levels of both IL-6 and sIL-6R. IL-6 levels were significantly elevated in schizophrenic patients compared to those in controls, whereas no significant difference in sIL-6R levels was observed between schizophrenic patients and controls. Our findings suggest that the presence of schizophrenia is associated with elevated IL-6 levels, whereas sIL-6R levels are mainly predetermined by the Asp358Ala genotype and are not associated with the disease status. Increased IL-6 levels without alterations in sIL-6R levels may result in excessive IL-6 signaling in schizophrenia.
最近的研究表明，白细胞介素-6（IL-6）信号过度激活在精神分裂症的发病机制中起作用。先前的研究报道了精神分裂症与白细胞介素-6 受体（IL-6R）基因 Asp358Ala 多态性之间存在显著关联，该多态性已知可调节健康受试者中循环 IL-6 和可溶性 IL-6R（sIL-6R）的水平。为了进一步研究该多态性在精神分裂症患者中的影响，我们比较了 Asp358Ala 多态性各基因型的精神分裂症患者和健康对照者的血浆 IL-6 和 sIL-6R 水平。在 104 例精神分裂症患者和 112 例健康对照者中进行了 Asp358Ala 基因分型和血浆 IL-6 水平测定。在这些参与者中，选择了 53 例精神分裂症患者和 49 例对照者进行血浆 sIL-6R 水平的测定。采用双向协方差分析，以转换后的血浆水平为因变量，诊断和基因型为自变量，性别和年龄为协变量。IL-6 和 sIL-6R 水平未观察到诊断×基因型的交互作用。Asp358Ala 的 Ala 等位基因与 IL-6 和 sIL-6R 的水平均显著相关。与对照组相比，精神分裂症患者的 IL-6 水平显著升高，而 sIL-6R 水平在精神分裂症患者和对照组之间无显著差异。我们的研究结果表明，精神分裂症的存在与 IL-6 水平升高有关，而 sIL-6R 水平主要由 Asp358Ala 基因型决定，与疾病状态无关。IL-6 水平升高而 sIL-6R 水平不变可能导致精神分裂症中过度的 IL-6 信号转导。
