Association between tumor necrosis factor-alpha promoter-308 A/G polymorphism and susceptibility to sepsis and sepsis mortality: A systematic review and meta-analysis

Objective. The tumor necrosis factor (TNF)-alpha promoter -308 A/G polymorphism has been reported to be associated with sepsis with inconsistent results. We conducted a systematic review and meta-analysis to determine whether the TNF-alpha -308 A/G polymorphism TNF2 (G/A or A/A) confers susceptibility to sepsis or is associated with increased risk of death from sepsis. Data Sources: We performed an electronic search of OVID MEDLINE from 1950 to June 2008 and EMBASE from 1980 to June 2008. Study Selection: From 1935 reviewed study articles, 25 were included based on predefined inclusion criteria. Data Extraction: Two reviewers independently extracted data onto standardized forms. Data Synthesis: An association between development of sepsis and the TNF2 genotype was found in the overall population (odds ratio, 2.15; 95% confidence interval, 1.45-3.19; p <.01). Strati- fication by ethnicity indicated that the contribution to this observation may be stronger among the Asian population (odds ratio, 3.16; 95% confidence interval, 1.92 to 5.20; p < .01) compared with other ethnicities. There was no association between the TNF2 genotype and mortality from sepsis (odds ratio, 1.48; 95% confidence interval, 0.81 to 2.70; p = .20). However, when stratified for ethnicity, there may be an increased risk for fatal outcomes among Asians (odds ratio, 10.75; 95% confidence interval, 2.98 to 38.78; p < .01). Conclusions: Our systematic review and meta-analysis demonstrates that the TNF2 polymorphism is associated with sepsis. However, TNF2 is not associated with sepsis mortality. (Crit Care Med 2010; 38:276-282)