Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections.
Human toll-like receptor 4 (hTLR4) and CD14 are known to be components of the lipopolysaccharide receptor complex. Our study investigated the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphism(s) with outcome in an intensive care unit (ICU) population at risk for sepsis. By use of a polymerase chain reaction-based restriction fragment-length polymorphism analysis technique, the hTLR4 gene was altered in 14 (18%) of 77 ICU patients (all positive for systemic inflammatory response syndrome) and in 5 (13%) of 39 volunteers. There was a significantly higher incidence of gram-negative infection among patients with the mutations (11 [79%] of 14), compared with that in the wild-type population (11 [17%] of 63; P=.004). No association between CD14 polymorphism(s) and the incidence of infection or outcome was observed. These findings indicate that hTLR4 mutations are associated with an increased incidence of gram-negative infections in critically ill patients in a surgical setting.
Agnese
Doreen M
DM
Division of Surgical Sciences, Department of Surgery, University of Medicine and Dentistry New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.
Calvano
Jacqueline E
JE
Hahm
Sae J
SJ
Coyle
Susette M
SM
Corbett
Siobhan A
SA
Calvano
Steve E
SE
Lowry
Stephen F
SF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004198:Disease Susceptibility; D029721:Drosophila Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D016905:Gram-Negative Bacterial Infections / Q000235:genetics*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D012307:Risk Factors; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors