肿瘤坏死因子-α基因启动子857位点单核苷酸多态性与强直性脊柱炎易感性的Meta分析

Association between tumor necrosis factor-alpha 857C/T polymorphism and susceptibility to ankylosing spondylitis: a meta-analysis

中文关键词:  强直性脊柱炎  肿瘤坏死因子α  单核苷酸多态性  Meta分析

英文关键词:Ankylosing spondylitis  Tumor necrosis factor-alpha  Single nucleotide polymorphism  Meta-analysis

中文摘要:

  【摘要】 目的：探讨肿瘤坏死因子（TNF）-α基因启动子-857位点单核苷酸多态性与强直性脊柱炎（AS）易感性的关联情况。方法：计算机检索PubMed、Cochrane Library、Ovid、中国生物医学文献数据库（CBM）、中国期刊全文数据库（CNKI）、万方数据库、维普数据库，检索时间均为建库至2013年10月，收集TNF-α-857位点单核苷酸多态性与AS易感性的病例-对照研究，利用Revman 5.2和Stata12.0软件进行统计分析。结果：共纳入9篇文献，包括933例患者（AS组）和1094例对照（对照组）。Meta分析结果显示CC基因型[OR=0.46，95%CI（0.26，0.81），P=0.007]、C等位基因[OR=0.61，95%CI（0.41，0.91），P=0.02]、T等位基因[OR=1.64，95%CI（1.10，2.43），P=0.02]在AS组与对照组比较差异均有统计学意义，但TT基因型[OR=1.49，95%CI（0.95，2.34），P=0.08]在两组间比较差异无统计学意义。除TT基因型（P=0.09，I2=42%）外，CC基因型（P<0.00001，I2=87%）、C等位基因（P<0.00001，I2=84%）和T等位基因（P<0.00001，I2=84%）在各研究间均有较明显的异质性。采用逐一剔除纳入研究的方法进行敏感性分析，各研究间仍有明显异质性。除TT基因型外，CC基因型、C等位基因、T等位基因与AS易感性的漏斗图均对称。CC基因型[Begg′s检验（z=0.52，P=0.602）；Egger′s检验（t=0.23，P=0.825）]、TT基因型[Begg′s检验（z=0.94，P=0.348）；Egger′s检验（t=1.26，P=0.248）]、C等位基因[Begg′s检验（z=0.31，P=0.754）; Eg?鄄ger′s检验（t=0.72，P=0.494）]、T等位基因[Begg′s检验（z=0.31，P=0.754）；Egger′s检验（t=－0.72，P=0.494）]的结果均无统计学意义。结论：TNF-α基因启动子-857位点CC基因型、C和T等位基因与AS易感性有关联性，携有T等位基因者患AS的风险增高。

英文摘要:

  【Abstract】 Objectives: To explore the association between the polymorphism in -857 site of tumor necrosis factor(TNF)-α promoter region and the susceptibility to ankylosing spondylitis(AS). Methods: Case-control studies Pubmed, Cochrane Library, Ovid, Chinese Biomedical Database(CBM), Chinese National Knowledge Infrastructure(CNKI), Wanfang and Weipu data bases from inception to October 2013 for the association between TNF-α-857 C/T polymorphism and the susceptibility to AS were collected. Meta-analysis was performed by Revman 5.2 and Stata 12.0 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were derived from random-effects or fixed-effects models to assess the strength of the association. Results: Nine case-control studies were included in the final meta-analysis, including a total of 933 AS patients and 1094 controls. Statistically significant differences between AS and control groups were observed in the susceptibility to AS and TNF-α-857 genotype CC [OR=0.46, 95%CI (0.26, 0.81), P=0.007], allele C [OR=0.61, 95%CI (0.41, 0.91), P=0.02] and T [OR=1.64, 95%CI (1.10, 2.43), P=0.02]. But, no statistical difference in the frequency of genotype TT [OR=1.49, 95%CI (0.95, 2.34), P=0.08] was observed between AS and control groups. There were obvious heterogeneities among the studies of genotype CC(P<0.00001, I2=87%), allele C(P<0.00001, I2=84%) and allele T(P<0.00001, I2 =84%), except genotype TT(P=0.09, I2=42%). Sensitivity analysis was performed by leaving out one study at a time, but the heterogeneity remained obvious. It was symmetric of the funnel plots of genotype CC, allele C and T with AS, but genotype TT. There was no statistical significance in genotype CC[Begg′s test(z=0.52, P=0.602), Egger′s test(t=0.23, P=0.825)], genotype TT[Begg′s test(z=0.94, P=0.348), Egger′s test(t=1.26, P=0.248)], allele C[Begg′s test(z=0.31, P=0.754), Egger′s test(t=0.72, P=0.494)] or allele T[Begg′s test(z=0.31, P=0.754), Egger′s test(t=－0.72, P=0.494)]. Conclusions: Genotype CC, allele C and T of TNF-α-857 are associated with the susceptibility to AS, and T-allele carriers have higher risk of AS.