白细胞介素6在云南汉族和哈尼族精神分裂症中的遗传机制及临床应用研究

Schizophrenia is a severe mental illness with high morbidity, recurrence rate and disability, however, the etiology of schizophrenia is still unclear. Systematic studies of schizophrenia is insufficient, especially the studies on the ethnic populations of Yunan province. Epidemiological studies indicated that the morbidity of schizophrenia in Hani people was significantly lower than the Han people in Yunnan province, the mechanism remain unknown. Research shows that interleukin 6 (IL-6) may play an important role in the pathogenesis of schizophrenia. Our previous work suggested that the sequence polymorphism of IL-6 is associated with schizophrenia in Yunnan. At the same time, we found that the expression of IL-6 in blood of patients with schizophrenia increased significantly in Yunnan, and the serum IL-6 levels could be decreased after 3 months of risperidone treatment. In this project, the genetic diversity analysis of IL-6 gene polymorphism in Han and Hani was studied by genetic association analysis and risperidone clinical treatment. It’s aim to find out genetic basis for low morbidity in Hani and determine the distribution frequency of IL-6 genotype associated with risperidone treatmenteffect between the Han and the Hani. Eventually, this project provide the basis for the individualized treatment of schizophrenia, and whether IL-6 is suitable as a biomarker for assessing the therapeutic effect of schizophrenia.

精神分裂症是一种病因未明的发病率、复发率、致残率均较高的重性精神疾病。云南人群，特别是少数民族人群精神分裂症的系统研究相对缺乏。流行病学研究显示云南哈尼族中精神分裂症的发病率显著低于汉族，原因尚不清楚。研究表明白细胞介素6（IL-6）可能在精神分裂症发病中扮演重要角色。我们前期研究发现IL-6序列多态性与云南精神分裂症具有相关性，同时IL-6在云南精神分裂症患者血液中的表达量显著升高，在利培酮治疗3个月后，患者血清中IL-6的含量显著降低。本项目拟通过群体水平的遗传相关性分析揭示IL-6基因序列多态性与云南汉族和哈尼族精神分裂症发生的相关性，并结合利培酮临床治疗研究，判断IL-6是否适合作为精神分裂症治疗效果评估的生物标志物。研究结果将有助于了解云南少数民族精神分裂症发生的遗传因素，为精神分裂症的个体化治疗提供科学依据。具有重要的科学意义和临床应用前景。

精神分裂症(Schizophrenia, SCZ)是一种病因未明的发病率、复发率、致残率高的重性精神疾病。同时，本病带来的个人负担及社会负担重，对医疗资源的消耗巨大。流行病学调查研究显示，精神分裂症大致占全球人口的1%，然而，其发病机制未明，且缺乏客观参考诊断指标，因而对疾病的防治带来诸多难题。本课题组在此项目的支持下，整合基因单核苷酸多态性，RNA-seq及分子生物学实验研究，发现rs10401120(TCF4)等位基因T及rs2295814(EGR2)等位基因A可能与精神分裂症易感性有关，而rs1877670(EGR3)等位基因C可能是本病的保护因素；同时，我们发现IL-6、IL-1β表达与SCZ的病情呈显著正相关，且二者可作为反应利培酮治疗有效性参考指标；最后，我们发现异常升高的IL-1β可能通过影响神经发育进而介导SCZ的发病过程。以上结果为未来关于精神分裂症易感基因的研究提供了一定的新视野，对精神分裂症的早期筛查具有重要参考价值，同时，针对IL-6、IL-1β的检测，在SCZ的临床实践中具有重要的参考与指导意义。