MCP-1基因-2518A/G多态性与葡萄膜炎易感性的Meta分析

Association of MCP-1-2518A/G polymorphism with uveitis susceptibility： a Meta-analysis

背景 近年来研究表明,单核细胞趋化蛋白1（MCP-1）基因多态性与葡萄膜炎易感性密切相关,然而目前国内外关于MCP-1基因-2518A/G多态性与葡萄膜炎发病风险的相关性尚未有一致结论.目的 系统评价MCP-1基因-2518 A/G多态性与葡萄膜炎易感性的关系.方法 按照检索策略,计算机检索PubMed、Embase、Web of Science、中国知网（CNKI）、维普网（VIP）、万方数据及中国生物医学文献数据库（CBD）,检索时限为建库起至2014年3月,收集关于MCP-1基因-2518A/G多态性与葡萄膜炎发病风险的相关文献,按照纳入及排除标准筛选文献、提取数据资料,并对纳入研究的文献进行质量评价.采用RevMan 5.2及Stata12.0软件进行Meta分析,计算合并效应量优势比（OR）值及其95％可信区间（CI）,并进行发表偏倚及敏感性分析.结果 共纳入8篇研究文献,累积病例1 197例,对照1 570例.MCP-1基因-2518A/G G和A、GG和AA及GG和AG＋AA基因型与总体葡萄膜炎发病风险均无明显相关性（均P＞0.05）,GG＋AG和AA基因型与总体葡萄膜炎发病风险具有显著相关性（P=0.01,OR=1.25,95％C1：1.06～1.48）,而敏感性分析结果显示二者无明显相关性（P=0.19,OR=1.16,95％ CI：0.93～1.45）.按葡萄膜炎类型进行亚组分析结果显示,携带等位基因G、GG基因型的个体罹患前葡萄膜炎的风险明显增高（G和A：P=0.01,OR=1.49,95％CI：1.16 ～1.90;GG和AA：P=0.01,OR=2.09,95％CI：1.21～3.61;GG＋AG和AA：P=0.01,OR=1.58,95％ CI：1.12～2.23;GG和AG＋AA：P=0.01,OR=1.78,95％CI：1.12 ～2.83）,且GG＋AG和AA基因型个体罹患白塞病的风险也明显增高（P=0.04,OR=1.35,95％CI：1.01～1.79）,而与其他类型葡萄膜炎发病风险无明显相关（P＞0.05）.按种族进行亚组分析结果显示,在黄种人群中,携带等位基因G、GG基因型的个体罹患葡萄膜炎的风险明显增高（G和A：P=0.04,OR=1.15,95％CI：1.01～1.32;GG和AA：P=0.04,OR=1.32,95％ CI：1.02 ～1.71;GG＋AG和AA：P=0.01,OR=1.36,95％CI：1.09～1.70）,而在白种人群中等位基因G、GG基因型与葡萄膜炎均无明显相关（均P＞0.05）.结论 MCP-1基因-2518A/G多态性与白塞病、前葡萄膜炎及黄种人群葡萄膜炎易感性有关,GG基因型及等位基因G可能是白塞病、前葡萄膜炎及黄种人群葡萄膜炎易感的危险因素.

Background Monocyte chemoattractant protein-1 （MCP-1） polymorphisms are demonstrated to be significantly associated with the susceptibility to uveitis in recent years,while a consistent conclusion for the association of MCP-1-2518A/G polymorphism and uveitis risk is not reached yet.Objective This study was to comprehensively investigate the correlation between MCP-1-2518A/G polymorphism and uveitis susceptibility.Methods General searches of electronic database including PubMed,Embase,Web of Science,CNKI,VIP,Wanfang database and China biomedical literature database （CBD） were performed to retrieve published case-control studies regarding the association between MCP-1-2518A/G polymorphism and uveitis risk.The data were screened according to the inclusion and exclusion criteria and extracted,and the quality of included studies was evaluated.The pooled odds ratios （OR） with 95% confidence intervals （CI） were calculated.Publication bias and sensitivity analysis were also assessed.All statistical analyses were conducted with RevMan 5.2 and Stata 12.0 software.Results A total of 8 eligible case-control studies involving 1 197 cases and 1 570 controls were included in the Meta-analysis.The results showed no significant association of MCP-1-2518A/G polymorphism with uveitis susceptibility in the G vs.A,GG vs.AA and GG vs.AG＋AA models （all at P〉0.05）.MCP-1-2518A/G polymorphism was found to be significantly associated with uveitis risk in the GG＋AG vs.AA model （P =0.01,OR =1.25,95% CI：1.06-1.48）,while no significant association was found by the sensitive analysis （GG ＋ AG vs.AA：P =0.19,OR =1.16,95% CI：0.93-1.45）.The subgroup analysis by uveitis types revealed that the individuals carrying allele-G or GG genotype harbored a significantly increased risk for anterior uveitis （G vs.A：P=0.01,OR=1.49,95% CI：1.16-1.90;GG vs.AA：P=0.01,OR=2.09,95% CI：1.21-3.61;GG＋AG vs.AA：P=0.01,OR=1.58,95% CI：1.12-2.23;GG vs.AG＋AA：P=0.01,OR=1.78,95% CI：1.12-2.83）.The individuals with GG＋AG vs.AA genotype harbored a significantly increased risk for Behcet＆#39;s disease （BD） （P=0.04,OR =1.35,95% CI：1.01-1.79） but not for other types of uveitis （P 〉 0.05）.Additionally,a significantly elevated risk was found in uveitis patients with allele-G or GG genotype in Asian population in the subgroup analysis based on ethnicity （G vs.A：P =0.04,OR =1.15,95% CI：1.01-1.32;GG vs.AA：P=0.04,OR=1.32,95% CI：1.02-1.71;GG＋AG vs.AA：P=0.01,OR =1.36,95% CI：1.09-1.70）,but that was not found in Caucasians population （all at P〉0.05）.Conclusions MCP-1-2518A/G polymorphism is significantly associated with the risk of uveitis in Asian population,anterior uveitis and BD.The allele-G or GG genotype may increase the risk of uveitis in Asian population,anterior uveitis and BD.