Association of tumour necrosis factor-α (TNF-α) gene polymorphisms (-308 G>A and -238 G>A) and the risk of severe dengue: A meta-analysis and trial sequential analysis

Abstract

Individual studies have assessed the association between TNF-α-308G>A and TNF-α-238 G>A polymorphisms and severity of dengue infection. However, the results are inconclusive and most studies had small sample sizes. The objective of this study was to summarize the evidence of association between TNF-α-308 G>A and TNF-α-238 G>A and severity of dengue infection.This study follows the preferred reporting items for systematic reviews and meta- analyses of genetic association studies, recommended by PLOS One. We calculated pooled odds ratio and its 95% confidence interval (CI) to estimate the association between TNF-α-308 G>A or TNF-α-238 G>A and the risk of severe dengue infections. To determine the information size required for this meta-analysis study, a trial sequential analysis (TSA) was done. Eight studies (640 cases and 1275 controls), which assessed the association of TNF-α-308 G>A or TNF-α-238 G>A and the risk of DHF were included. Overall, we found no significant association between TNF-α-308 G>A and the DHF risk in the allelic model (OR, 0.91; 95% CI, 0.51–1.63), the recessive model (OR,1.32;95%CI,0.73–2.37), the dominant model (OR,0.93;95%CI:0.59–1.47) or the additive model (OR,1.43,95;95%CI:0.79–2.59). There was also no significant association between TNF-α-238 G>A and DHF risk under the allele contrast model (OR:1.51;95%CI:0.88–2.58), the recessive model (OR,1.48,95% CI:0.33–6.58), the dominant model (OR,1.48;95%CI:0.56–3.92), or the additive model (OR:1.5;95%CI:0.34–6.69). On subgroup analysis, neither the Asian population nor the non-Asian population showed significant association between TNF-α-308 G>A/TNF-α-238 G>A and the DHF risk under any genetic models. Leave-one-out meta-analysis showed stability of the results. TSA plots suggested that the sample size in this meta-analysis study was below the required information size.The findings suggest an inclusive evidence of the association between TNF-α-308/ TNF-α-238 G>A and the risk of developing severe dengue infection. Large studies with evidence of Hardy-Weinberg equilibrium, assessing gene-gene interactions are recommended.

Investigation of TNF-α and DC-SIGN promoter polymorphisms in patients with dengue fever in Lahore city of Pakistan

“…They deduced that there is no association between these SNPs and dengue severity not only in Asian but also in other ethnic populations. 32 Another case-control study from Brazil supports our findings for TNF alpha-238 and -308 SNPs. They also did not find any association between these SNPs and DF.…”

Predictive markers for the early prognosis of dengue severity: A systematic review and meta-analysis

“…Notwithstanding, the conclusions went hand in hand with the study limitations that formed the body of evidence, say the combination of DHF and DSS or late measurement [12,14,19,22,23]. Besides, studies have focused concern on immunogenetic markers that benefit pathophysiology rather than medical case management [18,[24][25][26][27]. Here we advance the findings of prior work to illustrate the association of available markers and severe dengue in a different context.…”

Efficacy and safety of biologic agents for IgA nephropathy: A protocol for systematic review and meta-analysis

“…For the pooling of estimates across the included studies, the summary RRs and their 95% CIs will be calculated using a random effects model, based on the presence of statistical heterogeneity in the studies. Otherwise, a fixed effects model will be used [ 38 , 39 ].…”