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

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,...

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Bibliographic Details
Published in:European journal of clinical microbiology & infectious diseases 2009-09, Vol.28 (9), p.1055-1065
Main Authors: 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
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Bacterial diseases
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Child
Child, Preschool
Dentistry
Female
Gene Frequency
Genes
Genetic Predisposition to Disease
Haplotypes
Health care
Human bacterial diseases
Humans
Infant
Infant, Newborn
Infections
Infectious diseases
Internal Medicine
Leprosy
Leprosy - genetics
Leprosy - immunology
Male
Medical Microbiology
Medical research
Medical sciences
Medicine
Middle Aged
Mycobacterium
Mycobacterium leprae
Mycobacterium leprae - immunology
Pathogenesis
Polymorphism
Polymorphism, Single Nucleotide
Public health
Research centers
Toll-Like Receptor 4 - genetics
Tropical bacterial diseases
Tuberculosis
Tuberculosis and atypical mycobacterial infections
Tumor necrosis factor-TNF
Young Adult
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Summary: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 
ISSN:0934-9723
1435-4373
DOI:10.1007/s10096-009-0746-0