PTPN22基因变异及其调控信号通路在中国汉族人类风湿关节炎患者中的研究

Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic, systemic inflammatory disorder. The prevalence of the RA disease is about 0.2-0.4% in Han Chinese, of which more than 5 million have RA. Rheumatoid arthritis (RA) is a long-term disease that can be a disabling condition to lead to short average life expectancy of 10 to 15 years. Although the cause of RA is complex, genetic factors are known to be the major determinants of the susceptibility to RA, with an estimate of heritability of around 53-65%. The tyrosine phosphatase, non-receptor type 22 (PTPN22) mutation is reported to be related to rheumatoid arthritis (RA) in Caucasus population. Due to racial difference, however, it is unclear about the correlation between RA in Chinese Han ethnic population with PTPN22, and the possibility as a target of PTPN22 needs further study. Our laboratory focuses on the study of rheumatism related gene for a long time, and we propose that RA in Chinese Han population is probably independent for PTPN22 signal pathway in many patients. In this research, we’ll design a new method which is mixed-sample high-throughput deep sequencing combined with large-sample study to analysis the correlation between the PTPN22 and RA in Chinese Han population, and analyze the possible dysfunction of PTPN22 and signal pathway change in RA pathogenesis. This study will offer evidence for new approach to explore RA pathogenesis in Han Chinese and for new potential targets for RA treatment, which would improve the level of clinical diagnosis and treatment of RA . It is of great significance in reducing the RA morbidity and improving the life quality of RA patients.

类风湿关节炎是一种最常见的风湿病，其患病率高，致残率高。该病发病机制仍不明，已知遗传因素是其易感性的决定因素，特别是蛋白酪氨酸磷酸酶非受体型22(PTPN22)基因变异被证实与欧洲高加索人患病最相关。但我们的研究表明该基因在中国汉族人中与发病的相关性仍存争议(Arthritis & Rheumatology,2014；Nature,2014)，同期我们也发现新变异或低频率变异可以解释疾病易感性中以往未知的部分（(Arthritis & Rheumatology,2014)。故本研究拟结合深度测序和分子免疫学手段对PTPN22基因变异及其调控信号通路在汉族类风湿关节炎发病中的作用和机制进行深入研究，以解答这一关键问题，并评估该基因是否适合作为汉族人诊断和治疗靶点。本研究将为探索汉族人类风湿关节炎发病机理提供新的途径，也为治疗寻找新的靶点，对提高该病的临床诊治水平，改善患者预后，具有重要意义。