【作者】 李锋；

【导师】 杨森；

【作者基本信息】 安徽医科大学 ， 皮肤病与性病学， 2016， 硕士

【摘要】 研究背景系统性红斑狼疮(SLE)是一种慢性,复发性,多系统的自身免疫性疾病。系统性红斑狼疮的全球患病率约为20–150/100000。SLE好发于女性,特别是育龄期女性,男女比例为1:9。自身免疫抗体在SLE发病机制中扮演重要角色,疾病的临床表现多样化与包含抗体的免疫复合物的沉积导致的肾脏、大脑、皮肤以及其他器官系统炎症有关。遗传因素可能增加SLE进展的风险。全基因组关联分析在过去几年发现许多与SLE风险相关的遗传易感位点,如IRF5,ITGAM,STAT4,MECP2等。2012年,基于以往SLE GWAS研究的基础上,为了进一步发现疾病易感位点/基因,深入揭示SLE遗传学发病机制,相关课题组和香港大学SLE研究团队展开合作,利用中国大陆和中国香港汉族人SLE GWAS数据进行meta分析,并在中国大陆、中国香港和泰国的三个亚洲独立人群中进行大样本验证,发现一个新的易感位点rs6705628(2p13.1,TET3)和SLE显著关联,揭示了其在细胞周期调节、吞噬、DNA甲基化等机制在SLE发病中可能起着重要的作用。本研究通过测定在SLE患者以及正常对照中的TET3基因m RNA表达情况,来探讨TET3基因表达水平变化,与表型的关系以及其与发病可能的作用机制。目的探讨TET3基因在SLE患者与健康对照的外周血单个核细胞(PBMCs)中m RNA表达情况,探究TET3基因m RNA表达与SLE表型、活动度指数(SLEDAI)的相关性。方法收集SLE患者89例,正常对照85例,从外周血单个核细胞(PBMCs)中提取出m RNA,然后逆转录为complementary DNA(c DNA),加入相应的荧光染料、引物,利用ABI 7900HT高通量荧光定量PCR技术检测外周血单个核细胞中TET3基因m RNA的表达情况,收集整理所有实验数据,用SPSS22.0软件进行数据统计分析。结果SLE患者TET3基因m RNA表达水平高于正常对照组;TET3基因m RNA表达水平SLEDAI相关,以及与口腔溃疡、关节炎、抗ds DNA抗体、抗SM抗体相关,P值<0.05差异具有统计学意义。结论TET3基因表达水平差异提示其在SLE发病机制中可能起到某种重要的调节作用。更多还原

【Abstract】 Background Systemic lupus erythematosus(SLE) is a chronic, relapsing, multi system autoimmune disease. The global prevalence rate of SLE is about 20-150/100000. SLE occurs in women, especially women of childbearing age, male to female ratio is 1:9. Autoimmune antibodies play an important role in the pathogenesis of systemic lupus erythematosus(SLE), clinical manifestations are diverse,including immune complex deposition in the kidney, brain, skin and inflammation of other organ systems. Genetic factors may increase the risk of progression of SLE. Genome-wide association analysies in the past few years have found that more than 55 Genetic susceptibility loci associated with SLE, such as IRF5, ITGAM, STAT4, MECP2, and so on.In 2012, based on the former GWAS studies of SLE, in order to discover more disease susceptibility loci / genes, and reveal the genetic pathogenesis of SLE, associated research group cooperate with the Hong Kong University research team of SLE analysis the GWAS data by meta analysis, and identited in China’s mainland and Hong Kong, China and Thailand three Asian independent populations, found five novel loci, rs34330(12p13,CDKN1B), rs6705628(2p13.1, tet3),rs6804441(3q13, CD80), rs4622329(12q23, DRAM1) and rs4948496(10q21, ARID5B),which were significantly associated with SLE, revealing the mechanism of cell cycle regulation, phagocytosis, DNA methylation and so on, which has an important role in the pathogenesis of SLE.Objective To investigate the different expression levels of TET3 in peripheral blood mononuclear cells(PBMCs) from SLE patients and healthy controls and the association between TET3 expression and SLEDAI or the clinical phenotype of SLE.Method We performed a RT-PCR in 89 patients with SLE and 87 controls. We extracted m RNAs from the peripheral mononuclear cells(PBMCs), and then reverse-transcribed into complementary DNA(c DNA), adding the corresponding fluorescent dyes and primers. Using ABI 7900 HT high-throughput fluorescence quantitative PCR Technology to detect the expression of TET3 in peripheral blood mononuclear cells. Analysis was performed with Statistical Package for the Social Science(SPSS) version 22.0. Data were expressed as mean ± standard deviation. P value < 0.05(two-tailed) was considered to be statistically significant.Results The expression levels of TET3 m RNA in SLE patients were increased compared with healthy controls’,also foud oral ulcer 、arthritis、 ds DNA、SM and SLEDAI associated with the expression levels of TET3. P value < 0.05(two-tailed) was considered to be statistically significant.Conclusion These results indicated that TET3 m RNA may be correlated with the pathogenesis of SLE.更多还原