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.
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 illpatients. Genotyping this locus does not seem to be useful in predicting sepsis outcome.
Authors: B D Freeman; C R Kennedy; H L Frankel; B Clarridge; D Bolcic-Jankovic; E Iverson; E Shehane; A Celious; B A Zehnbauer; T G Buchman Journal: Pharmacogenomics J Date: 2009-12-08 Impact factor: 3.550