系统性红斑狼疮（SLE）是一种累及多脏器的自身免疫性疾病，遗传在其发病过程中起重要作用。申请人已完成大规模SLE全外显子组关联研究，发现4个新易感区域和3个编码变异。同时提示，CD58基因存在SLE潜在易感信号（P = 5.28E-08）；申请人深入研究，发现该关联信号在独立小样本汉族SLE病例-对照中被验证（P < 0.05），但在大样本欧洲人群却无统计学显著关联。据此推测，CD58基因区域可能存在汉族人特异性的SLE易感基因。为探索该区域与汉族人群SLE的关联并揭示其参与SLE的作用机制，拟采用Sequenom平台在6,000例SLE病例-对照对CD58基因变异进行分型，明确其与SLE发病风险的统计学关联；利用RT-PCR、eQTL、荧光素酶报告基因等，初步揭示SLE中该区域基因变异的作用机制。该研究预期将发现汉族人特异性易感基因，为SLE风险预测、诊疗和新药研发提供理论依据。

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs, and genetic factors play an important role in its pathogenesis. The applicant has performed a large-scale exome-wide study for SLE, which discovered four novel SLE gene regions encompassing three novel missense variants with genome-wide significance. In addition, we found a suggestive SLE susceptibility signal in CD58 gene almost reaching genome-wide significance in the SLE exome-wide study data (P= 5.28E-08). Then the applicant found that the correlation signal was verified in the independent small samples of SLE cases - control in Chinese population (P < 0.05), but there was no statistically significant correlation in the large samples of European population. Accordingly, we speculate that the CD58 gene may be SLE specific susceptibility region in Chinese population. In order to explore the correlation between this region and SLE and reveal the potential roles in the mechanism of SLE in Chinese population, we plan to perform a further replication study for SNPs in CD58 gene in 6,000 samples. Then, we will conduct some functional experiment to reveal the important role of CD58 in onset of SLE, such as RT-PCR, eQTL and dual luciferase assay. This study is expected to find the specific susceptibility genes for Chinese which can provide theoretical basis for prediction, diagnosis and drug targets of SLE.