A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis.
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 pr...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1797087545523175424 |
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| author | Hawn, T Dunstan, S Thwaites, G Simmons, C Thuong, N Lan, N Quy, H Chau, T Hieu, N Rodrigues, S Janer, M Zhao, L Hien, T Farrar, J Aderem, A |
| author_facet | Hawn, T Dunstan, S Thwaites, G Simmons, C Thuong, N Lan, N Quy, H Chau, T Hieu, N Rodrigues, S Janer, M Zhao, L Hien, T Farrar, J Aderem, A |
| author_sort | Hawn, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:37:09Z |
| format | Journal article |
| id | oxford-uuid:a92d5af4-fea8-4a93-b7fa-9110877e54bd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:37:09Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:a92d5af4-fea8-4a93-b7fa-9110877e54bd2022-03-27T03:06:37ZA polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a92d5af4-fea8-4a93-b7fa-9110877e54bdEnglishSymplectic Elements at Oxford2006Hawn, TDunstan, SThwaites, GSimmons, CThuong, NLan, NQuy, HChau, THieu, NRodrigues, SJaner, MZhao, LHien, TFarrar, JAderem, A 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. |
| spellingShingle | Hawn, T Dunstan, S Thwaites, G Simmons, C Thuong, N Lan, N Quy, H Chau, T Hieu, N Rodrigues, S Janer, M Zhao, L Hien, T Farrar, J Aderem, A 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. |
| title_full | A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. |
| title_fullStr | A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. |
| title_full_unstemmed | A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. |
| title_short | A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis. |
| title_sort | polymorphism in toll interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis |
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