银屑病是一种常见的免疫相关性多基因病，常累及皮肤、关节和甲。其病因尚未明确，严重危害患者身心健康。申请人一直从事银屑病遗传学研究，基于前期银屑病GWAS数据库，大样本量（8339病例，12185对照）深入发掘，发现银屑病新的易感基因LNPEP（非同义突变rs2303138，P=1.87E-12)。有研究表明该基因与银屑病公认易感基因MHC及ERAP1基因相互作用介导抗原呈递，激活NF-κB信号通路，且与糖尿病、高血压等银屑病伴发疾病的发病密切相关，提示LNPEP基因可能在银屑病发病机制中发挥重要作用。本研究拟通过对LNPEP基因测序搜寻疾病功能性变异，结合RT-PCR、EMSA实验、双报告基因及RNA干扰等功能学实验，在DNA、RNA及细胞水平上验证该基因与银屑病的关联性,提示其在银屑病发病中可能发挥的作用，结合既往发现易感基因的生物学特点，为揭示银屑病发病机制提供新的研究线索和理论依据。

Psoriasis is a common immune-mediated polygenic disease that affects the skin, nails and joints. The etiology remains unclear, and it severely affects physical and mental health of patients.The applicant has been endeavoring to the research of the pathogenesis of psoriasis for serveral years. Based on the previous psoriasis GWAS data，we further explore the susceptibility genes with a large sample size（8,339 cases and 12,185 controls）, and identified a new susceptibility gene LNPEP (non-synonymous mutation rs2303138, P=1.87E-12). Some research indicated that LNPEP gene was involved in immune antigen-presenting process through interacting with known psoriasis susceptibility genes MHC-I molecules and ERAP1, activated NF-κB signal pathway and also played a role in the development of diabetes and hypertension that associated with psoriasis. Therefore, It suggests LNPEP gene may play an important role in the pathogenesis of psoriasis. In order to further confirm the association between the LNPEP gene and psoriasis，and investigate the potential role of the gene in the development of psoriasis at the DNA, RNA and cellular level, we plan to perform LNPEP gene sequencing to search for the functional variants and conduct some functional experiment, such as RT-PCR, electrophoresis mobility shift assay (EMSA), luciferase double reporter gene experiments, RNA-mediated interference and so on. Combined with the biological features of previously identified psoriasis genes, it will provide new clues and theoretical basis for promoting the understanding of the pathogenesis of psoriasis.