發(fā)布時(shí)間：2018-05-25 18:27

  本文選題：系統(tǒng)性硬化癥 + 中國(guó)人群　； 參考：《北京協(xié)和醫(yī)學(xué)院》2010年博士論文

【摘要】：背景：系統(tǒng)性硬化癥(Systemic Sclerosis, SSc)是一種以組織纖維化、血管內(nèi)皮損傷和免疫系統(tǒng)激活為主要特點(diǎn)的結(jié)締組織疾病,臨床譜廣泛多樣,從皮膚硬化到肺動(dòng)脈高壓、肺纖維化、腎危象等致死性內(nèi)臟損害,為近來結(jié)締組織疾病中的研究熱點(diǎn)。該病病因和發(fā)病機(jī)制尚未明確,但已有研究表明遺傳因素占有重要的地位。國(guó)際上已先后對(duì)五十余個(gè)相關(guān)易感基因的單核苷酸多態(tài)性進(jìn)行了研究,但其中許多結(jié)果彼此矛盾。2009年以后,歐洲、美國(guó)、韓國(guó)等發(fā)表了大規(guī)模的全基因組關(guān)聯(lián)掃描(Genome Wide Association Study, GWAS)數(shù)據(jù),除進(jìn)一步驗(yàn)證了此前得到的若干個(gè)基因位點(diǎn)與疾病的強(qiáng)關(guān)聯(lián)外,還進(jìn)一步發(fā)現(xiàn)了新的位點(diǎn)。 目的：針對(duì)上述GWAS研究中得到的熱點(diǎn)候選基因及其相關(guān)位點(diǎn),研究中國(guó)人群系統(tǒng)性硬化癥的易感基因,并分析其與系統(tǒng)性硬化癥的不同表型間的關(guān)系。 方法：本研究采用Sequenom平臺(tái)對(duì)265名系統(tǒng)性硬化癥患者及122名正常對(duì)照的32個(gè)候選基因位點(diǎn)進(jìn)行了單核苷酸多態(tài)性的檢測(cè),對(duì)相關(guān)基因的等位基因和基因型的頻率進(jìn)行統(tǒng)計(jì)分析,并結(jié)合病例的臨床表現(xiàn)和血清抗體譜等,分析基因?qū)ο到y(tǒng)性硬化癥復(fù)雜表型的影響。 結(jié)果：MHC區(qū)rs7763822和rs7764491(p=0.004、p=0.0006)、STAT4rs7574865(p=0.027)與SSc有關(guān)；MHC區(qū)rs3128930、rs7763822、rs7764491與抗Sc1-70抗體有關(guān)(p分別為0.001、0.00001、0.00001)；BANK1rs17266594、STAT4rs7574865與ACA抗體有關(guān)(p=0.04、p=0.04); EXOF-IRF4rs12206548、rs2493040與分型有關(guān)(p=0.006、p=0.007)。 結(jié)論：STAT4可作為中國(guó)人群SSc的易感基因；MHC區(qū)基因與中國(guó)人群SSc關(guān)聯(lián)最強(qiáng);多個(gè)基因位點(diǎn)與SSc分型、抗Scl-70抗體和ACA抗體相關(guān)。
[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. 緇撴灉: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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