Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gram-negative infections

J Infect Dis. 2002 Nov 15;186(10):1522-5. doi: 10.1086/344893. Epub 2002 Oct 29.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Disease Susceptibility
  • Drosophila Proteins*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Gram-Negative Bacterial Infections / genetics*
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Male
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Mutation
  • Polymorphism, Genetic*
  • Receptors, Cell Surface / genetics*
  • Risk Factors
  • Toll-Like Receptor 4
  • Toll-Like Receptors


  • Drosophila Proteins
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors