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

Détails

Ressource 1Télécharger: serval:BIB_6D6AE35F8804.P001 (259.17 [Ko])
Etat: Public
Version: de l'auteur
Licence: Non spécifiée
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ID Serval
serval:BIB_6D6AE35F8804
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy.
Périodique
European Journal of Clinical Microbiology & Infectious Diseases
Auteur(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]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
28
Numéro
9
Pages
1055-1065
Langue
anglais
Résumé
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
Oui
Création de la notice
09/10/2009 12:53
Dernière modification de la notice
01/10/2019 6:18
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