Meta-analysis on the association TLR4 Asp299Gly polymorphism with ankylosing spondylitis
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摘要: 目的 采用Meta分析方法对TLR4基因Asp299Gly多态性与强直性脊柱炎(AS)的关系进行系统评价,探寻AS发病遗传背景的循证医学证据。 方法 以“强直性脊柱炎”和“toll样受体4或TLR4”和“多态性”为关键词,全面检索PubMed医学网站、中国学术期刊全文数据库、中国生物医学文献、万方等全文数据库,筛选TLR4基因多态性与AS关系的文献,截止2015年7月,筛选有详细信息的相关全文文献,根据是否为病例对照研究等纳入标准,对筛选文献中提供准确数据的文献进行Meta分析,根据资料有同质性,采用固定效应模型,合并OR值,采用Egger’s检验漏斗图对称性评价发表偏倚,系统评价TLR4基因Asp299Gly多态性与强直性脊柱炎的关联性。 结果 最终纳入6篇TLR4基因Asp299Gly多态性与强直性脊柱炎病例对照研究文献进行Meta分析,共计病例组851例,对照组842例。对照组人群均符合Hardy-Weinberg平衡。合并TLR4基因Asp299Gly位点的基因型(AG+GG)/AA,异质性检验Q检验统计量为5.82,I2=48.5%,P>0.05,采用固定效应模型进行统计分析,合并值OR=1.04(95%CI=0.70~1.54),差异无统计学意义(P>0.05),Egger’s检验漏斗图对称性,P>0.05,无发表偏倚。合并TLR4基因Asp299Gly位点的等位基因G/A,异质性检验Q检验统计量为6.80,I2=55.9%,P>0.05,采用固定效应模型进行统计分析,合并值OR=1.02(95%CI=0.70~1.50),差异无统计学意义(P>0.05)。Egger’s检验漏斗图对称性,P>0.05,无发表偏倚。 结论 尚不能认为TLR4基因Asp299Gly与AS易感性有关联。Abstract: Objective To investigate the association of Asp299Gly polymorphism in toll-like receptor 4(TLR4) gene with ankylosing spondylitis(AS) through meta-analysis for supplying evidences with evidence-based medicine in research of the genetic background of AS. Methods Literatures were initially retrieved from CBM disc,CNKI,WANGFANG DATA and PubMed by key words of "ankylosing spondylitis","toll-like receptor 4/TLR4 and polymorphism",and articles related to TLR4 Asp299Gly polymorphism and AS were available by July 2015.Eligible studies were defined as case-control study on full data included in the paper basis,and subjected to meta-analysis.Fixed effects model was used to pool the odd ratio(OR) by homogeneity in the data.Publication bias among the enrolled studies was evaluated using Egger' test to measure the funnel plot asymmetry.Systematic review was performed to estimate the relation of TLR4 Asp299Gly polymorphism with AS. Results Six studies related to TLR4 Asp299Gly polymorphism and AS were finally enrolled for current meta-analysis,involving 851 AS cases and 842 controls.The healthy controls in the 6 studies were agreed on Hardy-Weinberg equilibrium.Genotype distribution(AG+GG vs.AA) for TLR4 Asp299Gly allele was 5.82 by Q-test and I2 statistic to estimate the degree of heterogeneity(I2=48.5%,P>0.05).Fixed effects model estimation indicated pooled OR=1.04(95% CI=0.70-1.54,P>0.05).The difference was not significant.No publication bias was found by examining the funnel plot asymmetry using Egger' test(P>0.05).As for the allele G/A in TLR4 Asp299Gly,Q-test and I2 statistics showed 6.80(I2=55.9%,P>0.05).Fixed effects model revealed no significant difference(OR=1.02,95% CI=0.70-1.50,P>0.05).No publication bias occurred on allele G/A as the funnel plot asymmetry measured by Egger' test. Conclusion Current findings appear hard to determine the association of TLR4 Asp299Gly polymorphism with AS.
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Key words:
- TLR4 /
- Polymorphism /
- ankylosing spondylitis /
- Meta-analysis
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