CRTH2基因多态性与变应性鼻炎遗传易感性的关系及其致病机制研究

Allergic rhinitis (AR) occurs in a high frequency and severely health impair. The exact pathogenesis of allergic rhinitis remains unclear and genetic susceptibility is considered to be vital. CRTH2 is related to asthma and other allergic disease according to recent clinical studies. As an important immune receptor, CRTH2 is expressed on group 2 Innate lymphoid cells, mediate chemoattractant in allergic reaction. Previously, we identified the c.G1651A of CRTH2 may play an important role in AR. Based on the early results, we will further explore the relationship of c.G1651A and genetic susceptibility of AR through association analysis, investigate the biological mechanism of c.G1651A polymorphism in the regulation of CRTH2 gene transcription, and validate the functional results in vivo and in vitro. The purpose of this project is to find the potential mechanism of c.G1651A of CRTH2 in the pathogenesis of AR, which may shed a new light on the etiology of AR, and thus contribute to the diagnosis and treatment of AR.

变应性鼻炎的发病率高，危害严重，至今发病机制不明。目前研究认为遗传易感性和环境是该病发生的重要因素。近期研究发现CRTH2基因与哮喘等多种变应性疾病密切相关。CRTH2作为2型天然淋巴细胞(ILC)重要的分子标识，是变态反应中极为重要的受体类型，介导2型ILC细胞的炎性因子合成分泌及化学趋化作用。本课题组前期研究发现，CRTH2基因c.G1651A位点极有可能参与变应性鼻炎的发病。本课题拟在前期工作的基础上，通过对该位点深入的关联分析研究，确认该位点与变应性鼻炎遗传易感性的关系；同时通过对该位点进行功能学研究，从体内和体外水平进行验证，探讨该位点参与遗传易感性改变的致病机制。本课题的顺利开展将可能首次揭示CRTH2基因的个体遗传差异与变应性鼻炎遗传易感性的关系，深入探讨CRTH2基因参与变应性鼻炎的致病机制，为变应性鼻炎的机制理解及诊疗策略提供重要参考。