Roles of tumor necrosis factor alpha gene polymorphisms, tumor necrosis factor alpha level in aqueous humor, and the risks of open angle glaucoma: A meta-analysis

Purpose: This meta-analysis was performed to clarify the association between tumor necrosis factor alpha (TNF-alpha) gene polymorphisms and open angle glaucoma (OAG) risks, and the association between the TNF-alpha level in aqueous humor (AH) and the risks of glaucoma. Methods: 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-alpha 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-alpha levels in AH between patients with OAG and controls. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Results: 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-alpha -308G/A, -857C/T, -863C/A, and -238G/A polymorphisms and the risks of OAG, respectively. The combined results showed that the TNF-alpha -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-alpha 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. Conclusions: This meta-analysis suggests that patients with OAG may have higher TNF-alpha levels compared with the control subjects, and the TNF-alpha -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.