Common TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis.
BACKGROUND
Several studies have investigated single nucleotide polymorphisms (SNPs) in candidate genes associated with sepsis and septic shock with conflicting results. Only few studies have combined the analysis of multiple SNPs in the same population.


METHODS
Clinical data and DNA from consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-alpha, (TNF-alpha), interleukin-1 beta (IL-1 beta), plasminogen activator-1 (PAI-1), urokinase plasminogen activator (uPA), CD14 and toll-like receptor 4 (TLR4) was done.


RESULTS
Of 319 adults, 74% had sepsis, 19% had severe sepsis and 7% were in septic shock. No correlation between severity or outcome of sepsis was observed for the analyzed SNPs of TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 or TLR-4. In multivariate Cox proportional hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hospital mortality.


CONCLUSIONS
We did not find any association between TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms and outcome of Gram negative sepsis. Other host factors appear to be more important than the genotypes studied here in determining the severity and outcome of Gram negative sepsis.
Jessen
Kristine Marie
KM
Clinical Research Unit, Hvidovre University Hospital, Copenhagen, Denmark. s021726@student.dtu.dk
Lindboe
Sarah Bjerre
SB
Petersen
Anncatrine Luisa
AL
Eugen-Olsen
Jesper
J
Benfield
Thomas
T
D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000235:genetics* / Q000276:immunology; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000235:genetics* / Q000276:immunology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology; D012720:Severity of Illness Index; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood / Q000235:genetics*
D016207:Cytokines; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D017395:Plasminogen Activator Inhibitor 1; D011971:Receptors, Immunologic; C051321:SERPINE1 protein, human; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D014568:Urokinase-Type Plasminogen Activator