A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis

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dc.date.accessioned2018-09-14T11:15:03Z
dc.date.available2017-07-05T05:57:30Z
dc.date.available2006-06-16en_US
dc.date.available2006-06-16en_US
dc.date.available2006-06-16en_US
dc.date.available2006-06-16en_US
dc.date.available2006-06-16en_US
dc.date.available2006-06-16en_US
dc.date.available2006-06-16en_US
dc.date.available2006-06-16en_US
dc.date.available2018-09-14T11:15:03Z
dc.date.issued2006-10-15en_US
dc.description.abstractBACKGROUND: 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.
dc.identifier.urihttp://localhost:8080/dspace7/handle/123456789/173
dc.languageEnglishen_US
dc.titleA polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosisen_US
dc.typeJournal Article
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