Tumor necrosis factor gene polymorphism and septic shock in surgical infection

Objectives: To evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-α polymorphism with regard to the plasma TNF-α concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit (SICU). Design: A total of 112 postoperative critically ill infected patients were prospectively enrolled. Setting: SICU of a tertiary university-affiliated medical center. Patients: Patients who were consecutively admitted to the SICU because of surgical infection with sepsis. Intervention: Blood sampling. Measurements and Main Results: Blood sample was obtained 24 hrs after intensive care unit (ICU) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-α level and to analyze the genotype of the biallelic polymorphism of the TNF-α. Results: The allele frequency of the TNF2 in our infected ICU patients was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic shock during their ICU stay. Patients carrying the TNF2 allele were not more likely to develop septic shock, nor did they have a higher mortality rate. In the patients with septic shock, those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%, p < .05). In those who developed septic shock, the TNF2 allele was significantly associated with higher TNF levels. Conclusion: In patients admitted to SICU with surgical infection, the frequency of TNF2 allele was higher than in the general population. SICU patients with TNF2 allele did not show a higher incidence of developing septic shock, nor was there a higher baseline TNF-α level after infection. However, once septic shock had developed, the mortality rate was higher in those patients carrying the TNF2 allele.