The toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia

Tuberculosis (Edinb). 2004;84(6):347-52. doi: 10.1016/


Setting: Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. Studies in a murine model of pulmonary TB have identified a role for Toll-like receptor 4 (TLR4) in the development of chronic lung infection with Mycobacterium tuberculosis. The Asp299Gly polymorphism in the human TLR4 gene is associated with in vivo hyporesponsiveness to lipopolysaccharide (LPS) in Caucasians.

Objective: To determine whether TLR4 Asp299Gly influences LPS responses or susceptibility to pulmonary TB in humans in a Gambian population sample.

Design: We compared whole blood monokine responses to LPS in 245 healthy blood donors stratified by TLR4 Asp299Gly genotype to assess whether this polymorphism was functional in this population. A case-control study of 640 subjects was conducted to investigate whether TLR4 Asp299Gly was associated with TB.

Results: LPS-induced tumour necrosis factor, interleukin-1 beta and interleukin-10 production was not influenced by TLR4 Asp299Gly genotype. There was no association between TLR4 Asp299Gly and TB.

Conclusion: Our data suggest that TLR4 Asp299Gly has no influence on monocyte LPS responses or susceptibility to TB in Gambians and could be an ancient neutral polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Gambia
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Interleukin-1 / analysis
  • Interleukin-10 / analysis
  • Lipopolysaccharides / immunology*
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Polymorphism, Genetic / genetics
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / immunology
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tuberculosis, Pulmonary / ethnology
  • Tuberculosis, Pulmonary / genetics*
  • Tuberculosis, Pulmonary / immunology
  • Tumor Necrosis Factor-alpha / analysis
  • Up-Regulation


  • Interleukin-1
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10