Association between a genomic polymorphism within the CD14 locus and septic shock susceptibility and mortality rate

Objective: Genetic differences in immune responses may affect susceptibility to and outcome of septic shock. CD14 seems to be an important part of the innate immune system, initiating antimicrobial response. We evaluated the frequency of a recently discovered CD14 promoter gene polymorphism (C to T transition at base pair -159) among patients with septic shock compared with those in a control group. Design: Multiple-center study. Setting. Hospital research department. Patients: Ninety consecutive white patients with septic shock were included. The control group consisted of 122 age- and gender-matched white subjects. Interventions: In both groups, the C-159T CD14 promoter genetic polymorphism was determined by using polymerase chain reaction and subsequent Hae III restriction enzyme digestion of the polymerase chain reaction products. Measurements and Main Results: The C-159T polymorphism and the TT genotype were significantly overrepresented among septic shock patients compared with controls, Within the septic shock group, the mortality of patients with TT genotype (71%) was significantly higher than in patients with other genotypes (48%; Pearson chi-square, p=.008). In a multiple logistic regression model, the TT genotype was independently associated with an increased relative risk of death (odds ratio, 5.30; 95% confidence interval, 1.20-22.50, p=.02). Conclusions: The C-159T polymorphism affects susceptibility to septic shock and seems to be a new genetic risk factor for death.