中国汉族人群系统性硬化症的候选基因关联分析研究

发布时间：2018-06-16 04:17

  本文选题：单核苷酸多态性 + TNFSF4　； 参考：《北京协和医学院》2016年硕士论文

【摘要】：目的：系统性硬化症(Systemic sclerosis,SSc)是一种以纤维化为特征的自身免疫性疾病,遗传易感性在其发病机制中发挥重要作用。全基因组关联分析研究(genome-wide association study,GWAS)发现IRF5和IRF8基因均与白种人群中SSc患者相关。候选基因单核苷酸多态性(single-nucleotide polymorphisms,SNP)研究结果也显示TNFSF4,TNFAIP3,CCR6,IRF5,IRF8和ALK1基因的SNP位点和不同种族人群的多种自身免疫性疾病具有相关性,但其是否与中国汉族人群中的SSc患者相关目前尚未有研究报道。因此,本研究的目的是探讨TNFSF4,TNFAIP3,CCR,IRF5,IRF8和ALKI基因与中国汉族人群SSc及其不同的临床亚组之间的相关性,如SSc伴随抗拓扑异构酶I抗体(Anti-topoisomerase I,也称为抗Scl-70抗体)阳性组,SSc伴随肺间质病变(Interstitial lung disease,ILD)组和SSc伴随肺动脉高压(Pulmonary hYPertension,PAH)组。方法：本研究纳入了1030例SSc患者和1215例健康对照,采用基质辅助激光解吸电离飞行时间质谱(Matrix-Assisted Laser Desorption／Ionization Time of Flight Mass Spectrometry,MALDI-TOF MS)方法对如下6个基因所选14个SNP位点进行基因分型：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).结果：TNFSF4基因的位点rs844648等位基因和基因型频率都与SSc相关(p=1.7×10-3和p=5.0×10-3).TNFAIP3基因的位点rs6932056等位基因频率在疾病组和对照组之间有显著差异(p=5.0×10-3).TNFSF4其他三个位点(rsl234314,rs2205960和rs12039904)和TNFAIP3基因的rs5029939则与SSc表现出相对较弱的相关性(p0.05)。上述六个SNP位点均与SSc-ILD亚组具有相关性。TNFSF4基因的单体型rs1234314-rs2205960CG和GT以及rs12039904.rs844648CG和TA均与SSc具有相关性。CCR6基因的位点rs3093023等位基因频率和基因型频率均与SSc显著相关(p=3.2×10-3和p=7.6×10-3).CCR6基因的单体型rs3093023-rs1094621 6AT和GC与SSc同样具有相关性(p=8.6×10-3和p=0.03)。IRF5基因的SNP位点rs4728142在等位基因和基因型频率上与SSc显著相关(p=2.8×104和p=6.6×104),并且与抗SCL-70抗体阳性亚组和SSc-ILD亚组具有相关性(p=2.77×104和p=6.64×104)。ALK1基因的位点rs2277382仅与SSc-PAH亚组显著相关(p=7.2×10-3)。结论：本研究在中国汉族人群中开展,结果证实了TNFSF4,TNFAIP3,CCR6和IRF5基因与SSc具有相关性,CCR6基因可能与不伴随ILD和PAH的SSc亚组相关,IRF8基因可能与中国汉族人群不伴随PAH的SSc患者之间具有相关性,ALK1基因与SSc-PAH显著相关,CCR6, IRF8和ALK1基因可能是SSc或其临床亚组的易感基因。
[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. 閲囩敤鍩鸿川杈呭姪婵，

本文编号：2025263