本文選題：單核苷酸多態(tài)性 + TNFSF4��； 參考：《北京協(xié)和醫(yī)學院》2016年碩士論文

【摘要】：目的：系統(tǒng)性硬化癥(Systemic sclerosis,SSc)是一種以纖維化為特征的自身免疫性疾病,遺傳易感性在其發(fā)病機制中發(fā)揮重要作用。全基因組關聯(lián)分析研究(genome-wide association study,GWAS)發(fā)現(xiàn)IRF5和IRF8基因均與白種人群中SSc患者相關。候選基因單核苷酸多態(tài)性(single-nucleotide polymorphisms,SNP)研究結果也顯示TNFSF4,TNFAIP3,CCR6,IRF5,IRF8和ALK1基因的SNP位點和不同種族人群的多種自身免疫性疾病具有相關性,但其是否與中國漢族人群中的SSc患者相關目前尚未有研究報道。因此,本研究的目的是探討TNFSF4,TNFAIP3,CCR,IRF5,IRF8和ALKI基因與中國漢族人群SSc及其不同的臨床亞組之間的相關性,如SSc伴隨抗拓撲異構酶I抗體(Anti-topoisomerase I,也稱為抗Scl-70抗體)陽性組,SSc伴隨肺間質病變(Interstitial lung disease,ILD)組和SSc伴隨肺動脈高壓(Pulmonary hYPertension,PAH)組。方法：本研究納入了1030例SSc患者和1215例健康對照,采用基質輔助激光解吸電離飛行時間質譜(Matrix-Assisted Laser Desorption／Ionization Time of Flight Mass Spectrometry,MALDI-TOF MS)方法對如下6個基因所選14個SNP位點進行基因分型：TNFSF4(rsl234314,rs2205960,rs12039904和rs844648),TNFAIP3(rs5029939,rs6932056和rs5029937),CCR6(rs3093023,rs10946216和rs3093005),IRF5 (rs4728142),IRF8(rs11642873和rSl1117432)和ALKl(rs2277382).結果：TNFSF4基因的位點rs844648等位基因和基因型頻率都與SSc相關(p=1.7×10-3和p=5.0×10-3).TNFAIP3基因的位點rs6932056等位基因頻率在疾病組和對照組之間有顯著差異(p=5.0×10-3).TNFSF4其他三個位點(rsl234314,rs2205960和rs12039904)和TNFAIP3基因的rs5029939則與SSc表現(xiàn)出相對較弱的相關性(p0.05)。上述六個SNP位點均與SSc-ILD亞組具有相關性。TNFSF4基因的單體型rs1234314-rs2205960CG和GT以及rs12039904.rs844648CG和TA均與SSc具有相關性。CCR6基因的位點rs3093023等位基因頻率和基因型頻率均與SSc顯著相關(p=3.2×10-3和p=7.6×10-3).CCR6基因的單體型rs3093023-rs1094621 6AT和GC與SSc同樣具有相關性(p=8.6×10-3和p=0.03)。IRF5基因的SNP位點rs4728142在等位基因和基因型頻率上與SSc顯著相關(p=2.8×104和p=6.6×104),并且與抗SCL-70抗體陽性亞組和SSc-ILD亞組具有相關性(p=2.77×104和p=6.64×104)。ALK1基因的位點rs2277382僅與SSc-PAH亞組顯著相關(p=7.2×10-3)。結論：本研究在中國漢族人群中開展,結果證實了TNFSF4,TNFAIP3,CCR6和IRF5基因與SSc具有相關性,CCR6基因可能與不伴隨ILD和PAH的SSc亞組相關,IRF8基因可能與中國漢族人群不伴隨PAH的SSc患者之間具有相關性,ALK1基因與SSc-PAH顯著相關,CCR6, IRF8和ALK1基因可能是SSc或其臨床亞組的易感基因。
[Abstract]:Objective: systemic sclerosis (SSS) is an autoimmune disease characterized by fibrosis. Genetic susceptibility plays an important role in its pathogenesis. Genome-wide association study revealed that both IRF5 and IRF8 genes were associated with SSC in white population. The results of single-nucleotide polymorphisms (SNPs) of candidate genes also showed that the SNP loci of TNFSF4 / TNFAIP3 / CCR6 / IRF5 / IRF8 and ALK1 genes were associated with multiple autoimmune diseases in different ethnic groups. However, whether it is related to SSC patients in Chinese Han population has not been reported. Therefore, the purpose of this study was to investigate the relationship between TNFSF4, TNFAIP3, CCRRN5, IRF8 and ALKI genes and SSC and its different clinical subgroups in Chinese Han population. For example, SSC with anti-topoisomerase I (also known as anti-Scl-70 antibody) positive group with pulmonary interstitial lung disease (ILDD) and SSC accompanied pulmonary hypertension with pulmonary hypertension (pulmonary hypertension) group. Methods: 1030 SSC patients and 1215 healthy controls were included in this study. 閲囩敤鍩鴻川杈呭姪嬋，

本文編號：2025263