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

Journal article

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.

Authors: Newport, M; Allen, A; Awomoyi, A; Dunstan, S; McKinney, E

• Publication status: Published
• Journal: Tuberculosis (Edinburgh, Scotland)
• Volume: 84
• Issue: 6
• Pages: 347-352
• Publication date: 2004-01-01
• DOI: 10.1016/j.tube.2004.02.001
• EISSN: 1873-281X
• ISSN: 1472-9792
• Language: English
• Keywords: Adult; Case-Control Studies; Interleukin-10; Polymorphism, Genetic; Tumor Necrosis Factor-alpha; Up-Regulation; Receptors, Cell Surface; Gene Frequency; Genetic Predisposition to Disease; Adolescent; Interleukin-1; Genotype; Tuberculosis, Pulmonary; Toll-Like Receptor 4; Lipopolysaccharides; Male; Toll-Like Receptors; Gambia; Middle Aged; Humans; Membrane Glycoproteins