SOX9在VKH综合征黑色素脱失中的作用及分子机制研究

项目名称： SOX9在VKH综合征黑色素脱失中的作用及分子机制研究

项目编号： No.81200678

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 于红松

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： Vogt-小柳原田(VKH)综合征是我国常见致盲眼病，黑色素脱失是此病的重要特征，但机制尚不清楚。我们前期实验发现SOX9基因调控区SNP与VKH综合征显著相关，且患者SOX9基因的表达量及CD8+T细胞比例显著高于正常人。文献报道SOX9蛋白既是白癜风的自身免疫抗原，又能影响黑色素细胞的增殖和功能。据此推测，SOX9基因调控区SNP导致基因表达量增加，进而诱发自身免疫攻击黑色素细胞，参与VKH综合征黑色素脱失的发生。为证实此假设，本研究以SOX9基因为切入点，用大样本进一步确定调控区SNP与VKH综合征的相关性，从易感层面揭示其作用；探究SNP对基因转录和蛋白翻译的调控作用，以阐明调控区SNP的生物学功能；从细胞水平和动物实验两方面探讨SOX9蛋白对自身免疫攻击黑色素细胞的调控作用，揭示SOX9通过何种机制参与VKH综合征黑色素脱失临床表现的发生，为VKH综合征个体化防治提供新的靶点。

中文关键词： Beh？et病；VKH综合征；急性前葡萄膜炎；单核苷酸多态性；拷贝数变异

英文摘要： Vogt-Koyanagi-Harada (VKH) syndrome is a common blinding eye disease in China, and depigmentation is one of the most frequently seen clinical manifestations. However, the molecular mechanisms of depigmentation are still unknown. Our previous study showed that a SNP in SOX9 gene regulatory region was significantly associated with VKH syndrome, and the expression level of SOX9 gene and proportion of CD8+ T cell in VKH patients were significantly higher than those in healthy people. Other study identified that SOX9 was not only the vitiligo autoantigen in autoimmune polyendocrine syndrome type 1, but also could affected the proliferation and function of melanocytes. So it can be inferred that the SNP in SOX9 gene regulatory region may lead to increased gene expression level, then excess SOX9 protein may induce autoimmune attack against melanocytes and efficiently destruct them, and finally cause the depigmentation in VKH syndrome. In order to confirm this hypothesis, firstly, we take SOX9 gene as breakthrough point，then furtherly verify the correlation between SNP of SOX9 gene and VKH syndrome with larger samples, and reveal its role from susceptibility levels. Secondly, we explore the effects of SNP on gene transcription and translation function, elucidating the biological functions of the polymorphism. Finally, w

英文关键词： Beh？et disease；VKH syndrome；acute anterior uveitis；single nucleotide polymorphism；copy number variation