Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy.

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Serval ID
serval:BIB_6D6AE35F8804
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy.
Journal
European Journal of Clinical Microbiology & Infectious Diseases
Author(s)
Bochud P.Y., Sinsimer D., Aderem A., Siddiqui M.R., Saunderson P., Britton S., Abraham I., Tadesse Argaw A., Janer M., Hawn T.R., Kaplan G.
ISSN
1435-4373[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
28
Number
9
Pages
1055-1065
Language
english
Abstract
Accumulating evidence suggests that polymorphisms in Toll-like receptors (TLRs) influence the pathogenesis of mycobacterial infections, including leprosy, a disease whose manifestations depend on host immune responses. Polymorphisms in TLR2 are associated with an increased risk of reversal reaction, but not susceptibility to leprosy itself. We examined whether polymorphisms in TLR4 are associated with susceptibility to leprosy in a cohort of 441 Ethiopian leprosy patients and 197 healthy controls. We found that two single nucleotide polymorphisms (SNPs) in TLR4 (896G>A [D299G] and 1196C>T [T399I]) were associated with a protective effect against the disease. The 896GG, GA and AA genotypes were found in 91.7, 7.8 and 0.5% of leprosy cases versus 79.9, 19.1 and 1.0% of controls, respectively (odds ratio [OR] = 0.34, 95% confidence interval [CI] 0.20-0.57, P < 0.001, additive model). Similarly, the 1196CC, CT and TT genotypes were found in 98.1, 1.9 and 0% of leprosy cases versus 91.8, 7.7 and 0.5% of controls, respectively (OR = 0.16, 95% CI 0.06--.40, P < 0.001, dominant model). We found that Mycobacterium leprae stimulation of monocytes partially inhibited their subsequent response to lipopolysaccharide (LPS) stimulation. Our data suggest that TLR4 polymorphisms are associated with susceptibility to leprosy and that this effect may be mediated at the cellular level by the modulation of TLR4 signalling by M. leprae.
Pubmed
Web of science
Open Access
Yes
Create date
09/10/2009 12:53
Last modification date
01/10/2019 6:18
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