Objective: To investigate the influence of a lipopolysaccharide receptor CD14-159C/T genomic polymorphism on CD14 gene expression as well as protein release, and the relation of sepsis susceptibility and prognosis in patients with extensive burns.
Methods: The study group consisted of 26 patients with burns covering more than 30% of the total body surface area. The CD14 gene polymorphism was determined by polymerase chain reaction (PCR) and subsequent HaeIII restriction enzyme digestion of the PCR products. Meanwhile, the association of CD14, TNF-alpha mRNA expression in leukocytes and soluble CD14 (sCD14) levels in serum with CD14-159 polymorphism as well as prognosis after burns was also studied.
Results: The T allele frequencies in sepsis patients and non-survivors were higher than those in non-septic patients and survivors. The levels of CD14 mRNA, TNF-alpha mRNA expression and serum sCD14 were significantly different among patient groups with TT, TC, and CC genotypes. The above differences were also existed between survivors and non-survivors. CD14 mRNA expression was higher in heterozygotes (TT and TC) than in C homozygous patients (P < 0.05 or P < 0.01), and sCD14 level was higher in heterozygotes (TC) than C homozygous patients on day 7 postburn (P < 0.05). During the 28-day observation period, mean TNF-alpha mRNA expression was higher in patients homozygous for T allele than C homozygotes (P < 0.05). In addition, higher CD14 mRNA values were found in non-survivors compared to those in survivors on days 7 and 28 postburn (P < 0.05).
Conclusions: CD14C-159T polymorphism might markedly influence CD14 mRNA expression and sCD14 levels, and it seems to be associated with sepsis susceptibility and prognosis in patients with extensive burns. The T allele could be a genetic risk marker of adverse prognosis.
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Proc Natl Acad Sci U S A
February 2025
Molecular Genetics, Institute of Biology, Faculty of Life Sciences, Humboldt Universität zu Berlin, Berlin 10115, Germany.
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