【作者】 张鹏；

【导师】 张学军； 杨森；

【作者基本信息】 安徽医科大学 ， 皮肤病与性病学， 2011， 硕士

【摘要】 研究背景系统性红斑狼疮(Systemic lupus erythematosus, SLE)是一种累及多系统、多脏器、临床表现复杂多样的自身免疫性疾病,其特点是伴随大量抗体的产生。其发病机制迄今尚未完全阐明,遗传因素和环境因素在本病的发生发展中起着非常重要的作用。本课题组通过SLE全基因组关联分析(Genome-wide association study, GWAS)研究发现IRF5基因多态性与汉族人SLE呈显著性相关。目的对SLE发病年龄,蝶形红斑,盘状红斑,口腔溃疡,光敏感,关节炎,浆膜炎,肾脏病变,神经系统异常,免疫学异常,血液学异常,抗核抗体和血管炎进行分层分析,在中国汉族人群中研究IRF5( rs4728142)多态性与SLE患者临床表型的相关性,进一步阐明系统性红斑狼疮的发病机制,为SLE的治疗和防治提供新的思路,并为新治疗药物的研发提供理论依据。方法首先行病例-病例(如有蝶形红斑的患者和无蝶形红斑的患者)分析确定与SNP相关的临床表型,然后行病例-对照(如有蝶形红斑的患者/无蝶形红斑的患者和正常对照)分析进一步确定该SNP对不同临床表型所贡献的风险大小。本研究分析了风险等位基因与1997年美国风湿病学会(ACR)修订的SLE分类标准的11项临床表型、发病年龄和血管炎之间关联性。用SPSS13.0软件进行统计分析,算出P、95% CI、OR, P < 0.05认为有统计学意义。结果病例-病例分析结果示IRF5rs4728142与各表型无相关性(P值均>0.05),亚表型-对照分析表明rs4728142位点等位基因频率在大多数表型中分布存在显著性差异(P < 0.05),除了浆膜炎(+),rs4728142位点等位基因频率在浆膜炎(+)与正常对照之间分布无差异(OR = 1.21,95% CI: 1.00-1.48, P = 0.05),而在浆膜炎(-)与正常对照之间分布中有显著差异(OR = 1.45,95% CI:1.35-1.56,P = 4.53E-23)结论IRF5(rs4728142)基因多态性型与汉族人系统性红斑狼疮各临床表型无明显相关性。更多还原

【Abstract】 Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by autoantibodies production and multisystemic involvement. The exact etiology and pathogenesis is still not clear. Environmental and hereditary factors seem to play important roles in the development of the disease. We have identified susceptibility genes IRF5 for SLE in a recent genome-wide association study (GWAS) of Chinese Han population.Objective Here we investigated their relationships of the susceptibility genes with disease subphenotypes, including renal nephritis, photosensitivity, ANA, age at diagnosis, malar rash, discoid rash, immunological disorder, oral ulcer, hematological disorder, neurological disorder, serositis, arithritis and vasculitis to further clarify the pathogenesis of systemic lupus erythematosus, and bring theoretical basis to develope new drugs.Methods We first performed case-only analyses (e.g. presence of malar rash versus no malar rash) to identify which subphenotypes were associated with the specific SNPs. Then we performed subphenotype-control analyses (e.g. presence of photosensitivity or negative of photosensitivity versus health controls) to examine the risk conferred by the SNPs on different subtypes of SLE. We correlated the presence of risk alleles with total number of ACR criteria, age at diagnosis and vasculitis of SLE. P values, odd ratios (ORs) and 95% confidence interval (CI) were estimated using SPSS13.0 software, and P values below 0.05 were considered to be statistically significant.Results In Phenotype case-only analyses identified that IRF5 (rs4728142) was no significantly different in all phenotypes(P>0.05), In subphenotype–control analyses show that significantly different between most subphenotypes and healthy controls, except for Serositis:SNP rs4728142 showed an association only in patients without Serositis(OR = 1.45,95% CI:1.35-1.56,P = 4.53E-23) but not in the presence of Serositis(OR = 1.21,95% CI: 1.00-1.48,P = 0.05).Conclusions The results suggest that the polymorphism of IRF5 gene has no associationwith the Clinical Features of SLE in ChineseHan population.更多还原