Effect of the LT-alpha (+250 G/A) polymorphism on markers of inflammation and clinical outcome in critically ill patients.
BACKGROUND
Tumor necrosis factor alpha as a central mediator of the inflammation cascade is correlated to sepsis outcome. Tumor necrosis factor beta (LT-alpha) binds the same cell receptor and polymorphisms in both genes have been described. To evaluate the importance of the LT-alpha (+250 G/A) polymorphism for the clinical outcome of patients developing postsurgical sepsis, 85 patients were consecutively included into this study.


METHODS
Blood samples were obtained for analysis of the biallelic LT-alpha (+250 G/A) polymorphism and for determination of serum levels of sTNF-R1, TNF-alpha, IL-6, IL-8, IL-10, procalcitonin, and neopterin. Cytokine levels were measured repeatedly until the patients' discharge from the ICU.


RESULTS
The allele frequency was 0.28 for TNFB1 and 0.72 for TNFB2. The genotype distribution was TNFB1 homozygotes 4/79 (5.1%), TNFB1/TNFB2 heterozygotes 37/79 (46.8%), and TNFB2 homozygotes 38/79 (48.1%). Fifty-four out of 80 (67.5%) fulfilled the criteria for severe sepsis; 36/80 (45.0%) developed septic shock. Multiple organ failure occurred in 60/80 patients (75.0%), and the overall mortality was 26/80 (32.5%). Concerning the LT-alpha-genotypes, there was no difference in the frequency of severe sepsis or shock or in the development of multi-organ failure or death between the three subgroups. The peak plasma TNF-alpha levels were similar for all genotype subgroups.


CONCLUSIONS
There was no correlation between the biallelic LT-alpha (+250 G/A) polymorphism and the outcome of critically ill patients. Genotyping this locus does not seem to be useful in predicting sepsis outcome.
Rauchschwalbe
Sonja K
SK
Department of Surgery, University Hospital of Wuerzburg, Germany.
Maseizik
Thomas
T
Mittelkötter
Ulrich
U
Schlüter
Bernhard
B
Patzig
Christian
C
Thiede
Arnulf
A
Reith
H Bernd
HB
D000368:Aged; D016207:Cytokines / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011183:Postoperative Complications; D018805:Sepsis / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D012772:Shock, Septic / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha