PTTG1基因与银屑病发病机制相关性研究

Psoriasis is a serious skin disease that could affect the patients' healthy and appearance. It has long been widely accepted that psoriasis is a complex disease involving immune factors, multiple genetic and environmental factors. In the early GWAS and multistage replication studies, we have identified 6 new susceptibility loci associated to psoriasis in Chinese population, containing PTTG1 gene (P=1.1×10-8). As an oncogene, PTTG1 regulates bFGF, VEGF and IL-8 expression, which induce cell proliferation and promotes tumor formation. Notably, the PTTG1 region is now genetically implicated in both psoriasis and systemic lupus erythematosus (SLE). So we are going to further fine mapping PTTG1 and fully performing the SNP screening by using of automatic genotyping techniques, high throughout SNP scanning to identify the susceptibility SNP and causative mutation in the gene region. We will use the mRNA and protein expression technology, Yeast Two-hybrid System, interaction with proteins techniques to perform the function study for PTTG1 gene. This study is useful for understanding of the molecular mechanism of psoriasis and provide the evidences for risk prediction, diagnoses and prevention for psoriasis.

银屑病是一种严重影响患者身心健康的常见皮肤病，病因不明，大量研究表明本病是由免疫、遗传和环境等多种因素交互作用引起的复杂疾病。本课题组已完成中国人银屑病易感基因GWAS研究，继而在多区域多层次验证中发现了6个新的易感基因，其中PTTG1基因与银屑病显著相关（P=1.1×10-8）。作为一种癌基因，PTTG1通过调节bFGF,VEGF和IL-8表达，在人类细胞中促进肿瘤发生，且多项GWAS研究已证实PTTG1与系统性红班狼疮（SLE）有相关性，银屑病和SLE的发生存在相似的致病通路，因此推测PTTG1也与银屑病的发生相关。本研究拟运用高通量基因分型平台和测序技术，对覆盖基因区域内已知SNP点进行分型与测序，以精细定位并筛查其变异位点，并运用mRNA和蛋白表达、酵母双杂交等技术，探索PTTG1在mRNA、蛋白及细胞水平上的表达差异，揭示其与银屑病发病的相关性，为研究银屑病的发病机制提供依据。

银屑病是一种严重影响患者身心健康的常见皮肤病，病因不明，大量研究表明本病是由免疫、遗传和环境等多种因素交互作用引起的复杂疾病。本课题组前期已完成中国人银屑病易感基因 GWAS 研究，继而在多区域多层次验证中发现了 6 个新的易感基因，本研究在此基础上开展了IL-12B、PTTG1和GJB2基因与银屑病相关性研究及基因型表型分析，进行了IL23/Th17通路上5个SNP的联合效应分析，以及多个基因-基因及基因-环境因素交互作用分析，并且鉴定了银屑病易感基因LNPEP的错义突变rs2303138 (p.Ala763Thr)，从遗传学及生物信息学等多个角度研究分析揭示了银屑病发病机制的复杂性，开始为更加深入理解银屑病的发病通路、探索精准医疗的个体化生物学标记，基于对免疫机制的更全面的了解及确定治疗的新途径提供了依据。