大动脉炎(TA)是一种病因不明、预后极差的自身免疫性大血管炎。IL-6/IL-6R信号通路在多种自身免疫性疾病中发挥着重要作用。课题组前期对TA及健康对照进行关联分析发现，位于IL-6R基因第9位外显子的多态位点Asp358Ala（rs2228145）与汉族人群TA易感性显著相关，而与欧裔TA发病相关的IL-6基因与汉族人群TA无相关性。进一步研究发现IL-6R的Asp358Ala位点可参与IL-6R基因的选择性剪接模式，可能通过影响可溶型IL-6R的产生水平而对IL6信号通路的活化造成异常。然而Asp358Ala位点影响IL-6R选择性剪接的分子机制尚不清楚。本项目从Asp358Ala位点对IL-6R基因选择性剪接及相关剪接因子结合能力的影响入手，来研究IL-6R基因疾病相关位点的分子机制。本项目的开展可全面深入了解IL-6R基因与TA的分子作用机理，从新的角度了解TA的遗传因素。

Takayasu arteritis (TA) is an autoimmune large vessel vasculitis with unknown etiology and poor prognosis. The signaling pathway of IL-6/IL-6R plays an important role in multiple autoimmune diseases. The previous correlation analysis of TA and health controls has shown that polymorphic loci Asp358Ala (rs2228145), located in the ninth exons of the IL-6R gene, is significantly associated with susceptibility to TA in Chinese Han population, while the IL6 gene, associated with the pathogenesis of European TA, is not correlated with TA in the Chinese Han population. Further study found the Asp358Ala loci of IL-6R could participate in the alternative splicing process of IL-6R and affect the production level of soluble IL-6R, which leads to the abnormal activation of IL6 signaling pathway. Nevertheless, how the Asp358Ala loci affects the alternative splicing of IL-6R is not yet clear. In this study, we investigate the molecular mechanisms of disease-associated loci in IL-6R gene region through analyzing the effect of Asp358Ala loci on both the alternative splicing of IL-6R gene and the binding ability of IL-6R related splicing factors. Our study will not only offer comprehensive insights into the molecular mechanisms of IL-6R gene in TA, but also provide a new perspective to understand the genetic factors of TA.