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

Newport, M J, Allen, A, Awomoyi, A A, Dunstan, S J, McKinney, E, Marchant, A and Sirugo, G (2004) The toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia. Tuberculosis, 84 (6). pp. 347-352. ISSN 1472-9792

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Abstract

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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Primary Care and Public Health
Subjects: R Medicine > RC Internal medicine > RC0251 Constitutional diseases (General)
R Medicine > RC Internal medicine > RC0306 Tuberculosis
Depositing User: pam Thompson
Date Deposited: 09 May 2014 12:25
Last Modified: 09 May 2014 12:25
URI: http://sro.sussex.ac.uk/id/eprint/48387
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