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

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

Author information

1
Medical Research Council Laboratories, The Gambia. melanie.newport@cimr.cam.ac.uk

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.

PMID:
15525557
DOI:
10.1016/j.tube.2004.02.001
[Indexed for MEDLINE]

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