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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Polymorphisms in toll-like receptor 4 (TLR4) are associated with protection against leprosy
European Journal of Clinical Microbiology and Infectious Diseases, Volume 28, No. 9, Year 2009
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Description
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. © 2009 Springer-Verlag.
Authors & Co-Authors
Bochud, Pierre Yves
United States, Seattle
Institute for Systems Biology
Switzerland, Lausanne
Université de Lausanne Unil
Sinsimer, Daniel
United States, Newark
Public Health Research Institute
United States, New Brunswick
School of Graduate Studies
Aderem, Alan A.
United States, Seattle
Institute for Systems Biology
United States, Seattle
University of Washington
Siddiqui, Mahveen Ruby
United States, Newark
Public Health Research Institute
United Kingdom, London
Public Health England
Saunderson, Paul R.
Ethiopia, Addis Ababa
All Africa Leprosy
United States, Greenville
American Leprosy Missions
Britton, Sven
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Sweden, Stockholm
Karolinska Institutet
Abraham, Isaac
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
Tadesse Argaw, Azeb
Ethiopia, Addis Ababa
Armauer Hansen Research Institute
United States, New York
Icahn School of Medicine at Mount Sinai
Janer, Marta
United States, Seattle
Institute for Systems Biology
Hawn, Thomas Richard
United States, Seattle
Institute for Systems Biology
United States, Seattle
University of Washington
Kaplan, Gilla
United States, Newark
Public Health Research Institute
Statistics
Citations: 75
Authors: 11
Affiliations: 11
Identifiers
Doi:
10.1007/s10096-009-0746-0
ISSN:
09349723
Study Design
Cohort Study
Case-Control Study