Abstract
BackgroundThe -308G/A polymorphism in the gene encoding tumor necrosis factor-α (TNF-α) has been implicated in sepsis risk in many studies but with variable results. This study aimed to comprehensively assess the evidence of association between this polymorphism and risk of sepsis and sepsis-related mortality.Materials and MethodsPubMed, EMBASE and other databases were searched to identify relevant studies, and data were analyzed using Review Manager 5.0 and STATA 12.0.ResultsData from 34 publications involving 12,284 subjects were meta-analyzed. Combined analysis revealed an association between TNF-α -308G/A gene polymorphism and risk of sepsis (AA+GA vs. GG, OR 1.35, 95% CI 1.10–1.67, P = 0.005). This association was observed in the Caucasian subgroup (OR 1.50, 95% CI 1.13–2.00, P = 0.006), but not in the Asian subgroup. Across the entire study population, the polymorphism was also significantly related to septic shock risk (OR 1.52, 95% CI 1.18–1.95, P = 0.001) but not to sepsis-related mortality (OR 0.99, 95% CI 0.71–1.40, P = 0.97).ConclusionsThis meta-analysis suggests that the -308G/A gene polymorphism in the TNF-α gene may contribute to risk of sepsis and septic shock, but not risk of mortality.
Highlights
Sepsis, which is usually caused by infection and mediated by severe systemic inflammation, creates a heavy disease burden worldwide
Combined analysis revealed an association between tumor necrosis factor-α (TNF-α) -308G/A gene polymorphism and risk of sepsis (AA+GA vs. GG, odds ratio (OR) 1.35, 95% confidence interval (CI) 1.10–1.67, P = 0.005)
Across the entire study population, the polymorphism was significantly related to septic shock risk but not to sepsis-related mortality
Summary
Sepsis, which is usually caused by infection and mediated by severe systemic inflammation, creates a heavy disease burden worldwide. Singlenucleotide polymorphisms (SNPs) in the genes encoding these cytokines may be related to the risk of sepsis, and may even play roles in its pathogenesis [2, 3] Among these diverse cytokines, tumor necrosis factor-α (TNF-α) has attracted considerable attention. TNF-α is an intensively studied pro-inflammatory cytokine released mainly by activated neutrophils and macrophages that helps regulate the mammalian immune response and cellular homeostasis [4]. It stimulates various immune and structural cells, triggering release of large amounts of inflammatory mediators, which amplify the inflammatory response and cause severe systemic inflammation, eventually leading to sepsis [5]. This study aimed to comprehensively assess the evidence of association between this polymorphism and risk of sepsis and sepsis-related mortality
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