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A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis.
Title | A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Hawn, TR, Dunstan, SJ, Thwaites, GE, Simmons, CP, Thuong, NThuong, Lan, NThi Ngoc, Quy, HThi, Chau, TThi Hong, Hieu, NT, Rodrigues, S, Janer, M, Zhao, LPing, Hien, TTinh, Farrar, JJ, Aderem, A |
Journal | J Infect Dis |
Volume | 194 |
Issue | 8 |
Pagination | 1127-34 |
Date Published | 2006 Oct 15 |
ISSN | 0022-1899 |
Keywords | Adult, Asian Continental Ancestry Group, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Male, Mycobacterium tuberculosis, Polymorphism, Genetic, Receptors, Interleukin-1, Toll-Like Receptors, Tuberculosis, Meningeal, Tuberculosis, Pulmonary, Vietnam |
Abstract | BACKGROUND: Although meningitis is the most severe form of infection caused by Mycobacterium tuberculosis, the immunopathogenesis of this disease is poorly understood. We tested the hypothesis that polymorphisms in Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP), an adaptor protein that mediates signals from Toll-like receptors activated by mycobacteria, are associated with susceptibility to tuberculosis (TB). METHODS: We used a case-population study design in Vietnam with cord-blood control samples (n = 392) and case patients (n = 358) who had either pulmonary (n = 183) or meningeal (n = 175) TB. RESULTS: The TIRAP single-nucleotide polymorphism (SNP) C558T was associated with increased susceptibility to TB, with a 558T allele frequency of 0.035 in control samples versus 0.074 in case patients (odds ratio [OR], 2.25; P < .001). Subgroup analysis revealed that SNP 558T was more strongly associated with susceptibility to meningeal TB (OR, 3.02; P < .001) than to pulmonary TB (OR, 1.55; P = .22). In comparison to the 558CC genotype, the 558TT genotype was associated with decreased whole-blood interleukin-6 production, which suggests that TIRAP influences disease susceptibility by modulating the inflammatory response. CONCLUSIONS: These results provide the first evidence of an association of a TIRAP SNP with the risk of any disease and also suggest that the Toll-like receptor pathway influences susceptibility to meningeal and pulmonary TB by different immune mechanisms. |
DOI | 10.1086/507907 |
Alternate Journal | J. Infect. Dis. |
PubMed ID | 16991088 |