Associations of tumor necrosis factor-α-308 polymorphism with dengue infection: A systematic review and meta-analysis

Inconsistency of reported associations between the tumor necrosis factor-alpha-308 (TNF alpha-308) polymorphism (rs1800629) and dengue virus infection prompted a meta-analysis, to obtain more precise estimates. A literature search yielded 14 case-control studies. We calculated pooled odds ratios (OR) and 95% confidence intervals in three groups according to severity, dengue fever (DF), dengue hemorrhagic fever (DHF) and dengue (DEN) using standard genetic models. Pooled ORs were subjected to modifier treatment where re-analysis was confined to Hardy-Weinberg compliant (HWC) studies. Heterogeneity of outcomes warranted examining their sources with outlier treatment. In subgroup analysis, we compared Asian and South/Central American (SCA)/Brazilian effects. Overall pooled outcomes yielded no significant effects (OR 0.66-1.44, P = 0.08-0.96). In the dominant-codominant model, pooled effects were heterogeneous (I-2 = 47%-71%) which was lost/reduced (I-2 = 0%-43%) when outlier treatment was applied. This also yielded significant associations (OR 0.68-0.77, P = 0.02-0.05). Our results are best seen in the Asian subgroup, which in itself already yielded significant effects in DEN (OR 0.62-0.67, P = 0.01-0.02). These reduced risk findings were significant from the tests of interaction (P = 0.001-0.02) which highlights the protective effects of TNFa-308 among Asians. TNFa-308 effects on dengue are based on significance and non-heterogeneity of the post-outlier outcomes in the dominant and codominant models. Here, pooled effects may also be ethnic specific, where Asians are protected but not SCA. Both modified and Asian effects are up to 38% protective.