The G-->A single nucleotide polymorphism at the -308 position in the tumor necrosis factor-alpha promoter increases the risk for severe sepsis after trauma.
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-alpha 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.


CONCLUSIONS
The A-allele at the -308 position in the tumor necrosis factor-alpha promoter increases the risk for severe sepsis and possibly for death after trauma.
O'Keefe
Grant E
GE
Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9158, USA. grant.o'keefe@utsouthwestern.edu
Hybki
Dixie L
DL
Munford
Robert S
RS
D000328:Adult; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D018805:Sepsis / Q000209:etiology* / Q000235:genetics* / Q000401:mortality; D015599:Trauma Severity Indices; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014947:Wounds and Injuries / Q000150:complications* / Q000401:mortality
D014409:Tumor Necrosis Factor-alpha