Xin Xiangyang, Gao Lili, Wu Tong, Sun Fengyuan
First Center Clinical College, Tianjin Medical University, Tianjin, P R China.
Mol Vis. 2013;19:526-35. Epub 2013 Feb 27.
This meta-analysis was performed to clarify the association between tumor necrosis factor alpha (TNF-α) gene polymorphisms and open angle glaucoma (OAG) risks, and the association between the TNF-α level in aqueous humor (AH) and the risks of glaucoma.
A computerized literature search was performed for the relevant available studies from three databases including PubMed, ISI Web of Science, and Embase. The fixed or random effect model was selected based on the heterogeneity test using the Q test and the I(2) statistic. The associations between TNF-α gene polymorphisms and OAG risks were estimated by calculating pooled odds ratios (ORs) and the 95% confidence interval (CI), while a pooled standardized mean difference with 95% CI was used for the comparison of TNF-α levels in AH between patients with OAG and controls. Publication bias was estimated using Begg's funnel plots and Egger's regression test.
A total of 14 (1,182 cases and 3,003 controls), five (808 cases and 1,039 controls), three (645 cases and 666 controls), and three studies (404 cases and 625 controls) were finally included in the analyses for the associations between TNF-α -308G/A, -857C/T, -863C/A, and -238G/A polymorphisms and the risks of OAG, respectively. The combined results showed that the TNF-α -308G/A gene polymorphism was significantly associated with risks of high-tension glaucoma (A versus G: OR=1.660, 95% CI=1.033-2.667; AA/AG versus GG: OR=1.713, 95% CI=1.10-2.651), but not with normal tension glaucoma or exfoliation glaucoma. Ethnicity-stratified analysis revealed that a significant association also existed in Asians (A versus G: OR=1.947, 95% CI=1.097-3.456; AA/AG versus GG: OR=1.949, 95% CI=1.140-3.332). None of the other polymorphisms was significantly associated with OAG risks. Furthermore, the pooled results of six studies showed that the TNF-α levels in the AH of patients with OAG was higher than that of the control subjects (standardized mean difference=0.517, 95% CI=0.207-0.826, p=0.001). Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test.
This meta-analysis suggests that patients with OAG may have higher TNF-α levels compared with the control subjects, and the TNF-α -308G/A polymorphism is significantly associated with the risks of high-tension glaucoma. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.
进行此项荟萃分析以阐明肿瘤坏死因子α（TNF-α）基因多态性与开角型青光眼（OAG）风险之间的关联，以及房水（AH）中TNF-α水平与青光眼风险之间的关联。
通过计算机检索三个数据库（包括PubMed、ISI Web of Science和Embase）中的相关可用研究。根据使用Q检验和I²统计量的异质性检验选择固定效应模型或随机效应模型。通过计算合并比值比（OR）和95%置信区间（CI）来估计TNF-α基因多态性与OAG风险之间的关联，而使用合并标准化均数差及95%CI来比较OAG患者与对照组AH中TNF-α水平。使用Begg漏斗图和Egger回归检验评估发表偏倚。
最终分别纳入14项研究（1182例病例和3003例对照）、5项研究（808例病例和1039例对照）、3项研究（645例病例和666例对照）以及3项研究（404例病例和625例对照）分析TNF-α -308G/A、-857C/T、-863C/A和-238G/A多态性与OAG风险之间的关联。合并结果显示，TNF-α -308G/A基因多态性与高眼压性青光眼风险显著相关（A与G相比：OR = 1.660，95%CI =
1.033 - 2.667；AA/AG与GG相比：OR = 1.713，95%CI = 1.10 - 2.651），但与正常眼压性青光眼或剥脱性青光眼无关。种族分层分析显示，在亚洲人中也存在显著关联（A与G相比：OR = 1.947，95%CI = 1.097 - 3.456；AA/AG与GG相比：OR = 1.949，95%CI = 1.140 - 3.332）。其他多态性均与OAG风险无显著关联。此外，六项研究的合并结果显示，OAG患者AH中的TNF-α水平高于对照组（标准化均数差 = 0.517，95%CI = 0.207 - 0.826，p = 0.001）。漏斗图和Egger检验表明，所有比较中的发表偏倚可能性较低。
此项荟萃分析表明，与对照组相比，OAG患者可能具有更高的TNF-α水平，且TNF-α -308G/A多态性与高眼压性青光眼风险显著相关。由于无法完全排除潜在混杂因素，需要进一步研究来证实这些结果。
