Influence of the TNF-alpha and TNF-beta polymorphisms upon infectious risk and outcome in surgical intensive care patients.
BACKGROUND
Tumor necrosis factor-alpha (TNF-alpha) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-alpha and TNF-beta genes (TNF2 and LTA + 250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-alpha and -beta genes are associated with an increased risk of infection in an at-risk surgical intensive care population.


METHODS
Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing.


RESULTS
Eighty-six percent of the patients were TNF1 homozygotes (G:G at -308 of the TNF-alpha promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-beta, whereas the homozygous A:A was present in 45.4% of the patients.


CONCLUSIONS
The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.
Calvano
Jacqueline E
JE
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903, USA.
Um
John Y
JY
Agnese
Doreen M
DM
Hahm
Sae J
SJ
Kumar
Ashwini
A
Coyle
Susette M
SM
Calvano
Steve E
SE
Lowry
Stephen F
SF
D000368:Aged; D001483:Base Sequence; D003422:Critical Care; D016638:Critical Illness; D003428:Cross Infection / Q000150:complications / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk; D018805:Sepsis / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D012772:Shock, Septic / Q000235:genetics / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha