Association of Tumor Necrosis Factor-Alpha-308 G/A and -238 G/A Polymorphism with Diabetic Retinopathy: A Systematic Review and Updated Meta-Analysis

Background: Mounting evidence has suggested that tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR (the OR [95% CI] of [GA vs. GG], [GA + AA] vs. GG, and [A vs. G] are 1.21 [1.04, 1.41], 1.20 [1.03, 1.39], and 1.14 [1.01, 1.30], respectively). And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was a mild correlation in the entire group (the OR [95% CI] of [GA vs. GG] is 1.55 [1.14, 2.11]), which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.