TNF-TNF-α-308G/A-308G/A多态性与炎症性肠病易感性的Meta分析

Association between the-308G/A Polymorphism of TNF-α and Susceptibility of Inflammatory Bowel Disease:A Meta-analysis

目的系统评价肿瘤坏死因子-α(TNF-α)-308G/A多态性与炎症性肠病发病风险的相关性。方法计算机检索Pub Med、EMbase、CNKI、Wan Fang Data、CBM和VIP数据库,查找关于TNF-α-308G/A多态性与炎症性肠病易感性的病例-对照研究,检索时限均从建库至2015年1月25日。由2位评价员按照纳入与排除标准独立筛选文献、提取资料并评价纳入研究的方法学质量后,采用Rev Man 5.2和Stata 12.0软件进行Meta分析。结果最终纳入20个研究,共计2 860例患者和5 033例对照。Meta分析结果显示:与基因型GG比较,基因型GA、AA、GA+AA会增加溃疡性结肠炎的发病风险[GA vs.GG:OR=1.45,95%CI(1.02,2.07),P=0.04;AA vs.GG:OR=2.01,95%CI(1.32,3.05),P=0.001;GA+AA vs.GG:OR=1.51,95%CI(1.07,2.13),P=0.02];与基因型GA+GG比较,基因型AA会增加溃疡性结肠炎的发病风险[AA vs.GA+GG:OR=1.92,95%CI(1.26,2.91),P=0.002];等位基因A与溃疡性结肠炎发病风险无关。与基因型GG比较,基因型AA会增加克罗恩病的发病风险[AA vs.GG:OR=1.49,95%CI(1.07,2.08),P=0.02];与基因型GA+GG比较,基因型AA会增加克罗恩病的发病风险[AA vs.GA+GG:OR=1.50,95%CI(1.08,2.09),P=0.02]。基因型GA、GA+AA及等位基因A与克罗恩病发病风险无关。按人种来源的亚组分析显示,欧洲人TNF-α-308G/A基因多态性与炎症性肠病相关。结论现有证据表明,TNF-α-308G/A基因多态性与炎症性肠病易感性相关,基因型GA、AA、GA+AA均会增加溃疡性结肠炎的发病风险;基因型AA会增加克罗恩病的发病风险。鉴于纳入研究数量有限,上述结论尚需开展更多研究予以验证。

Objective To systematically review the tumor necrosis factor-α（TNF-α）-308G/A polymorphism and the risk of inflammatory bowel disease（IBD）. Methods All eligible case-control studies published up to Jan 25th2015 were identified by searching Pub Med, EMbase, CNKI, Wan Fang Data, CBM and VIP databases. Two reviewers independently screened the studies according to the inclusion and exclusion criteria, extracted data and assessed methodological quality of included studies. Then, meta-analysis was performed using Rev Man 5.2 and Stata 12.0 softwares. Results A total of 20 studies involving 2 860 IBD cases and 5 033 controls were included. The results of metaanalysis showed： Compared with the wild genotype GG, genotype GA, AA and genotype GA＋AA were associated with susceptibility of ulcerative colitis（UC）（GA vs. GG： OR=1.45, 95%CI 1.02 to 2.07, P=0.04; AA vs. GG： OR=2.01, 95%CI 1.32 to 3.05, P=0.001; GA＋AA vs. GG： OR=1.51, 95%CI 1.07 to 2.13, P=0.02）; Compared with genotype GA＋AA, genotype AA increased the risk of UC（AA vs. GA＋GG： OR=1.92, 95%CI 1.26 to 2.91, P=0.002）; allele A did not increase the risk of UC; Compared with genotype GG, genotype AA increased the risk of Crohn disease（CD）（AA vs. GG： OR=1.49, 95%CI 1.07 to 2.08, P=0.02）; Compared with genotype GA＋GG, while genotype AA increased the risk of CD（AA vs. GA＋GG： OR=1.50, 95%CI 1.08 to 2.09, P=0.02）; genotype GA, GA＋AA and allele A did not increase the risk of CD. In stratification analyses by ethnicity, we found that the TNF-α-308G/A was significat associated with IBD in Europeans. Conclusions Current evidence indicates that TNF-α-308G/A polymorphism is associated with the susceptibility of IBD, genotype GA, AA and GA＋AA increase the risk of suffering from UC while genotype AA increase the risk of suffering from CD. Due to the limited quantity of the included studies, more researches are needed to verify the above conclusion.