中国汉族重型痤疮易感基因CDH13功能及致病机制研究

重型痤疮是一种严重影响容貌、给患者带来巨大身心危害并造成社会问题的常见遗传皮肤病，明确致病机制是临床早期诊断及有效治疗的瓶颈。申请人前期通过全基因组关联分析及单倍型一致性分析等多种生物信息学的研究，发现CDH13基因可能是中国汉族重型痤疮新的易感基因，但CDH13在重型痤疮中的表达、功能及致病机制尚未明确。本项目将通过临床样本分析CDH13 及其配体脂联素的局部及系统表达水平与重型痤疮的相关性；明确CDH13及其配体的表达对角质形成细胞增殖等生物学功能的影响；并进一步阐明CDH13基因是否通过PI3K/AKT/mTOR信号通路影响角质形成细胞增殖从而参与重型痤疮的发生，最终揭示CDH13基因在重型痤疮发生中的致病机制，为中国汉族重型痤疮早期诊断、试剂盒开发及靶向治疗提供理论依据。

Severe acne is a common, harm, complex major diseases which bring physical and psychological effects on patients. It also cause society problems. Studies have shown that acne is a polygenic disease and genetic factor plays an important role in severe acne. Our previous work identified a new susceptibility genes (CDH13) confer risk to severe acne by IBD mapping analysis together with independent genotyping validation and potential gene–gene interactions research. We will carry detect the system and local expression of the new susceptibility genes in patient and controls, and also demonstrate functions and pathophysiologic mechanisms of gene CDH13 in severe acne. These works will provide an important evidence for the pathogenesis of severe acne, as well as the research and development of early diagnostic reagents for the disease.