The G→A Single Nucleotide Polymorphism at the –308 Position in the Tumor Necrosis Factor-α Promoter Increases the Risk for Severe Sepsis after Trauma

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Abstract
Background Clinical factors do not adequately explain why some patients develop severe sepsis after trauma and why others do not. We sought to determine whether genetic factors contribute to this risk. Methods Patients admitted to a single Level I trauma center were enrolled and DNA was isolated from leukocytes. The risk for severe sepsis and for death associated with polymorphism in the tumor necrosis factor-α promoter was determined by multivariate analysis. Results One hundred fifty-two patients had a 24% incidence of severe sepsis and a 13% case fatality rate. The A-allele was most common at the −308 position (n = 35). A-allele carriage at this location was associated with an adjusted odds ratio of 4.6 (95% confidence interval, 1.9–10.9) for severe sepsis and of 2.1 (95% confidence interval, 0.6–7.3) for death. Conclusion The A-allele at the −308 position in the tumor necrosis factor-α promoter increases the risk for severe sepsis and possibly for death after trauma.