中国人群系统性硬化症患者易感基因筛选初步结果

发布时间：2018-05-25 18:27

  本文选题：系统性硬化症 + 中国人群　； 参考：《北京协和医学院》2010年博士论文

【摘要】：背景：系统性硬化症(Systemic Sclerosis, SSc)是一种以组织纤维化、血管内皮损伤和免疫系统激活为主要特点的结缔组织疾病,临床谱广泛多样,从皮肤硬化到肺动脉高压、肺纤维化、肾危象等致死性内脏损害,为近来结缔组织疾病中的研究热点。该病病因和发病机制尚未明确,但已有研究表明遗传因素占有重要的地位。国际上已先后对五十余个相关易感基因的单核苷酸多态性进行了研究,但其中许多结果彼此矛盾。2009年以后,欧洲、美国、韩国等发表了大规模的全基因组关联扫描(Genome Wide Association Study, GWAS)数据,除进一步验证了此前得到的若干个基因位点与疾病的强关联外,还进一步发现了新的位点。 目的：针对上述GWAS研究中得到的热点候选基因及其相关位点,研究中国人群系统性硬化症的易感基因,并分析其与系统性硬化症的不同表型间的关系。 方法：本研究采用Sequenom平台对265名系统性硬化症患者及122名正常对照的32个候选基因位点进行了单核苷酸多态性的检测,对相关基因的等位基因和基因型的频率进行统计分析,并结合病例的临床表现和血清抗体谱等,分析基因对系统性硬化症复杂表型的影响。 结果：MHC区rs7763822和rs7764491(p=0.004、p=0.0006)、STAT4rs7574865(p=0.027)与SSc有关；MHC区rs3128930、rs7763822、rs7764491与抗Sc1-70抗体有关(p分别为0.001、0.00001、0.00001)；BANK1rs17266594、STAT4rs7574865与ACA抗体有关(p=0.04、p=0.04); EXOF-IRF4rs12206548、rs2493040与分型有关(p=0.006、p=0.007)。 结论：STAT4可作为中国人群SSc的易感基因；MHC区基因与中国人群SSc关联最强;多个基因位点与SSc分型、抗Scl-70抗体和ACA抗体相关。
[Abstract]:Background: systemic sclerosis (SSC) is a connective tissue disease characterized by tissue fibrosis, vascular endothelial injury and immune system activation. Its clinical spectrum is diverse, from skin sclerosis to pulmonary hypertension, pulmonary fibrosis. Fatal visceral damage, such as renal crisis, has been a hot topic in recent connective tissue diseases. The etiology and pathogenesis of the disease are not clear, but genetic factors have been shown to play an important role. The single nucleotide polymorphisms of more than 50 associated susceptibility genes have been studied internationally, but many of the results are contradictory. After 2009, Europe, the United States, Large scale Genome Wide Association Study, GWAS) data have been published in South Korea, which not only further verify the strong association of several previously obtained gene loci with disease, but also further discover new loci. Aim: to study the susceptible genes of systemic sclerosis in Chinese population and to analyze the relationship between these genes and the phenotypes of systemic sclerosis. Methods: in this study, 32 candidate loci of 265 patients with systemic sclerosis and 122 normal controls were detected for single nucleotide polymorphism (SNP) using Sequenom platform. The alleles and genotypes of the related genes were statistically analyzed. The effects of gene on complex phenotypes of systemic sclerosis were analyzed. 缁撴灉:MHC鍖簉s7763822鍜宺s7764491(p=0.004,p=0.0006),STAT4rs7574865(p=0.027)涓嶴Sc鏈夊叧;MHC鍖簉s3128930,rs7763822,rs7764491涓庢姉Sc1-70鎶椾綋鏈夊叧(p鍒嗗埆涓，

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