OBJECTIVE: To investigate the clinical relevance of the TLR4 11367 polymorphism in patients with major trauma. DESIGN: Genetic functional and association study. SETTING: Daping Hospital and Chongqing Emergency Medical Center, Chongqing, China. PATIENTS: A total of 132 patients with major trauma were prospectively recruited. MAIN OUTCOME MEASURES: The TLR4 11367 polymorphism was genotyped using single-tube, bidirectional, allele-specific amplification method. Whole peripheral blood samples obtained within 24 hours after admission were stimulated with lipopolysaccharide and then tested for production of tumor necrosis factor alpha and interleukin 6. Sepsis morbidity rate and multiple organ dysfunction scores were assessed. RESULTS: The 11367 polymorphism was shown to be strongly associated with less capacity of peripheral leukocytes to produce tumor necrosis factor alpha and interleukin 6 in response to ex vivo lipopolysaccharide stimulation in patients with trauma at admission. Results from association study indicated that patients with trauma who carry the 11367C allele were less likely to have sepsis and multiple organ dysfunction. CONCLUSIONS: Combined with our previous in vitro functional study, the results suggest that the TLR4 11367 polymorphism might be a good predictor of who is more likely to develop complications such as sepsis or multiple organ dysfunction syndrome, depending on genotype.
OBJECTIVE: To investigate the clinical relevance of the TLR4 11367 polymorphism in patients with major trauma. DESIGN: Genetic functional and association study. SETTING: Daping Hospital and Chongqing Emergency Medical Center, Chongqing, China. PATIENTS: A total of 132 patients with major trauma were prospectively recruited. MAIN OUTCOME MEASURES: The TLR4 11367 polymorphism was genotyped using single-tube, bidirectional, allele-specific amplification method. Whole peripheral blood samples obtained within 24 hours after admission were stimulated with lipopolysaccharide and then tested for production of tumor necrosis factor alpha and interleukin 6. Sepsis morbidity rate and multiple organ dysfunction scores were assessed. RESULTS: The 11367 polymorphism was shown to be strongly associated with less capacity of peripheral leukocytes to produce tumor necrosis factor alpha and interleukin 6 in response to ex vivo lipopolysaccharide stimulation in patients with trauma at admission. Results from association study indicated that patients with trauma who carry the 11367C allele were less likely to have sepsis and multiple organ dysfunction. CONCLUSIONS: Combined with our previous in vitro functional study, the results suggest that the TLR4 11367 polymorphism might be a good predictor of who is more likely to develop complications such as sepsis or multiple organ dysfunction syndrome, depending on genotype.
Authors: Maik Hüttemann; Stefan Helling; Thomas H Sanderson; Christopher Sinkler; Lobelia Samavati; Gargi Mahapatra; Ashwathy Varughese; Guorong Lu; Jenney Liu; Rabia Ramzan; Sebastian Vogt; Lawrence I Grossman; Jeffrey W Doan; Katrin Marcus; Icksoo Lee Journal: Biochim Biophys Acta Date: 2011-07-13