ERAP1基因与中国汉族人银屑病相关性研究

Psoriasis is a common chronic recurrent polygenic disease..To explore additional susceptibility genes for psoriasis, we performed a multistage.association study based on our first-stage GWAS that first discovered non-autoimmune.susceptibility gene LCE. ERAP1 was identified as a new susceptibility gene for.psoriasis in international cooperation through the large sample size. Besides, the.result was also validated in Uighur, European and American populations. MHC is an.internationally recognized susceptibility gene for psoriasis, especially for.early-onset psoriasis. In terms of gene function, ERAP1 is closely associated with.MHC class I molecules. And our research team found that ERAP1 is association with.early-onset psoriasis, which is consistent with MHC. Therefore, the further study.for ERAP1 is expected to reveal the pathogenesis of psoriasis (especially early-onset.psoriasis). In order to indentify genetic variations, which are directly related.to pathogenicity. We plan to sequence ERAP1 through ABI3730 in 2000 samples, and.perform replication study in additional 10000 samples. Furthermore, we plan to.perform some function experiments, such as the luciferase double reporter gene.experiments, CHIP experiments, immunohistochemistry and Western-blotting, to reveal.the specific role of ERAP1 in the pathogenesis of psoriasis. This study will provide.a new theoretical basis for the pathogenesis of psoriasis, risk prediction and.diagnosis and treatment.

银屑病是一种常见慢性复发性多基因遗传病。本课题组在前期GWAS首次发现非免疫性易感基因LCE的基础上，深入发掘GWAS数据，通过大样本量国际合作，发现新易感基因ERAP1，该结果也在中国维吾尔族和欧美人群中得到验证。ERAP1基因功能上与MHC I类分子有密切联系，MHC为国际公认的银屑病易感基因，对早发型银屑病作用显著，与本课题组发现ERAP1基因与早发型银屑病相关的结果刚好吻合。因此对该基因进一步研究有望为揭示银屑病（尤其是早发型银屑病）发病机制提供新的契机。本研究拟采用ABI3730对2000例样本的ERAP1基因进行测序，再通过对10000例样本的验证研究，鉴定与致病直接相关的遗传变异，采用萤光素酶双报告基因实验、CHIP实验、免疫组织化学、Western－blotting等方法揭示ERAP1基因在银屑病发病中的具体作用，为银屑病发病机制研究、风险预测和诊断治疗提供新的理论依据。

银屑病是一种常见慢性复发性多基因遗传病。本课题组在前期GWAS研究基础上，对发现的易感基因ERAP1进行深入研究。项目组采用ABI3730对2000例样本的ERAP1基因进行测序，再通过对10000例样本的验证研究，发现与银屑病相关的外显子区域编码变异。采用免疫组织化学、Western-blotting等功能学研究方法揭示ERAP1基因在银屑病发病中的具体作用。课题组同时开展了与ERAP1相关的易感基因深入研究，完成了银屑病易感基因HLA-C、ERAP1、TNFAIP3和TRAF3IP2之间的交互作用分析，银屑病易感基因NFKB1、BRAP 和GJB2基因型-表型分析，并发现新的易感基因LNPEP及其外显子区域编码变异与银屑病相关。为深入理解银屑病发病机制奠定了理论基础，为银屑病药物靶点研发、疾病预防与诊疗提供新的视角，同时进一步推进了银屑病遗传学研究和精准医学研究进程。