Lack of association between TLR4 Asp299Gly and Thr399Ile polymorphisms and sepsis susceptibility: A meta-analysis

Sepsis, a condition of systemic inappropriate inflammation response to the invasion of microorganisms, results in considerable morbidity and mortality in patients. Some, but not all, epidemiological studies have suggested that Toll-like receptor 4 (TLR4) polymorphisms, Asp299Gly and Thr399Ile, may influence the risk of at-risk patients for sepsis. Our work tried to further study the association of the two common polymorphisms with sepsis susceptibility by performing a meta-analysis of previous data. Electronic searches of MEDLINE, EMBASE and Web of Science databases were performed. Original observational studies dealing with the association between polymorphisms Asp299Gly and/or Thr399Ile and sepsis risk were selected. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects model or fixed-effects model based on the heterogeneity analysis. Seventeen studies including 2212 cases and 3880 controls were included with most subjects of Caucasian ethnicity. The odds ratio for the association of Asp299Gly polymorphism with sepsis risk was 1.22 (95% CI: 0.90–1.65, P = 0.21), and the association of Thr399Ile polymorphism was 1.16 (95%CI: 0.70–1.91, P = 0.57). Subgroup analysis and sensitivity analysis did not change the results. Our meta-analysis revealed that the two common TLR4 polymorphisms, Asp299Gly and Thr399Ile, have no strong association with the likelihood of sepsis in Caucasian populations. Further studies are needed to investigate the effect of genetic networks and their mutual interactions in TLR4 signaling pathway on sepsis susceptibility.

► A meta-analysis included 17 studies of 2212 cases and 3880 controls.
► Relations of Asp299Gly and Thr399Ile polymorphisms with sepsis risk were evaluated.
► The results showed no statistical significance under different comparison models.
► These two polymorphisms have no strong association with sepsis risk in Caucasian.