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TNF-α-308G/A基因多态性与TNF-α抑制药治疗类风湿关节炎疗效相关性的Meta分析
Association Between TNF-α Promoter-308 G/A Polymorphism and Response to TNF-α Inhibitors in Rheumatoid Arthritis: A Meta-analysis
  
DOI:
中文关键词:  肿瘤坏死因子-α-308 G/A  类风湿关节炎  肿瘤坏死因子抑制药  Meta分析  单核苷酸基因多态性
英文关键词:Tumor necrosis factor α 308 G/A  Rheumatoid arthritis  TNF α inhibitors  Meta analysis  Single nucleotide gene polymorphism
基金项目:国家自然科学基金项目(编号:81673246)
作者单位
白冰清1 辛芳冉1 魏婷婷1 付凌雨1,2 1.中国医科大学附属第一医院临床流行病与循证医学教研室 沈阳 1100012.中国医科大学附属第一医院病案管理中心 
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中文摘要:
      摘 要 目的:系统评价类风湿关节炎(RA)患者肿瘤坏死因子(TNF)-α 基因启动子区域-308 G/A单核苷酸多态性与TNF-α抑制药治疗有效性的关系。方法:计算机检索PubMed、Embase、The Cochrane Library、Web of Science、CNKI、WanFang Data、VIP数据库,搜集对比TNF-α-308 G/A基因多态性与TNF-α抑制药疗效相关性的队列研究或随机对照试验,检索时限均为建库至2018年6月。由两名研究员独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果:共纳入20项研究,包括3 280例病例。Meta分析结果显示,①TNF-α-308 GG基因携带者使用TNF-α抑制药(包括英夫利昔单抗、依那西普、阿达木单抗)治疗RA的疗效显著优于TNF-α-308 GA/AA基因携带者[OR=1.44,95%CI(1.05,1.97),P=0.02];②在亚洲人群中,TNF-α-308 G/A基因多态性与TNF-α抑制药治疗RA疗效的关联性有统计学意义[OR=3.13,95%CI(1.50,6.54),P=0.002];③依那西普治疗携带TNF-α-308 GG基因型的RA患者疗效显著优于携带TNF-α-308 GA/AA基因的患者[OR=1.71,95%CI(1.10,2.65),P=0.02]。结论:TNF-α-308 G/A基因多态性与TNF-α抑制药治疗RA的疗效有相关性,TNF-α-308 G/A影响亚洲人群的TNF-α抑制药疗效,依那西普治疗RA的疗效与该基因的关联有显著性,分析结果稳健性差,可能存在发表偏倚。
英文摘要:
      ABSTRACT Objective: To systematically review the relationship between tumor necrosis factor (TNF)-α gene promoter 308 G/A single nucleotide polymorphism(SNP) and the efficacy of TNF-α inhibitors in patients with rheumatoid arthritis. Methods:Database including PubMed, Embase, The Cochrane Library, Web of Science, CNKI, WanFang Data and VIP database were searched to collect cohort studies or randomized controlled trials about the relationship between TNF-α-308 G/A gene polymorphism and the efficacy of TNF-α inhibitors. The searching time was from inception to June 2018. Two researchers independently screened literature, extracted data and assessed the risk of bias of included studies. Then Meta analysis was performed by RevMan 5.3 software. Results:A total of 20 cohort studies involving 3 280 patients were finally included. The results of Meta analysis showed that: ①The efficacy of TNF-α inhibitors (including infliximab, etanercept and adalimumab) to TNF-α-308 GG carriers with rheumatoid arthritis were superior to TNF-α-308 GA/AA carriers (OR=1.44, 95%CI 1.05 to 1.97,P=0.02). ②TNF-α-308 G/A was associated with the efficacy of TNF-α inhibitors in Asians (OR=3.13, 95%CI 1.50 to 6.54, P=0.002). ③ Etanercept was more effective in treating patients with TNF-α-308 GG gene than TNF-α-308 GA/AA (OR=1.71, 95%CI 1.10 to 2.65, P=0.02). Conclusion:TNF-α-308 G/A gene polymorphism was associated with the efficacy of TNF-α inhibitors in rheumatoid arthritis treatment. The efficacy of TNF-α inhibitors were more superior on treating Asian patients with TNF-α-308 GG gene than TNF-α-308 GA/AA. The efficacy of Etanercept to TNF-α-308 GG carriers with rheumatoid arthritis were superior to TNF-α-308 GA /AA carriers.
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