Tumor necrosis factor‐α −308G/A and −238G/A polymorphisms are associated with increased risks of sepsis: evidence from an updated meta‐analysis

Previous studies have reported the relationship between tumor necrosis factor‐α (TNF‐α) ?308G/A and ?238G/A polymorphisms and sepsis risk with inconsistent results. The aim of this study was to estimate the association of the two polymorphisms with risk of sepsis or sepsis‐related mortality using a meta‐analysis. PubMed, Embase, and Web of Science databases were searched up to June 20 2016. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed or random effect model. Twenty‐six studies were included in this meta‐analysis. Overall, an increased sepsis risk of TNF‐α ?308G/A was observed (GA vs GG: OR = 1.43, 95% CI: 1.07–1.92; GA/AA vs GG: OR = 1.42, 95% CI: 1.06–1.89). Subgroup analyses showed that the significant association was found in Asians (GA vs GG: OR = 1.63, 95% CI: 1.01–2.63) and adult patients. Similarly, an increased sepsis risk of TNF‐α ?238G/A was observed in overall and subgroup analyses. However, no significant association was found between TNF‐α ?308G/A and ?238G/A polymorphisms and sepsis‐related mortality. These findings indicate that both TNF‐α ?308G/A and ?238G/A polymorphisms were associated with increased risks of sepsis but not sepsis‐related mortality. Further studies with larger sample size are needed to confirm these results.