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 pro...
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| Format: | Journal Article |
| Langue: | anglais |
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2018
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| Accès en ligne: | https://demo7.dspace.org/handle/123456789/173 |
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| _version_ | 1860822453200093184 |
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| author | Simmons, Cameron |
| author_browse | Simmons, Cameron |
| author_facet | Simmons, Cameron |
| author_sort | Simmons, Cameron |
| collection | DSpace |
| 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. |
| format | Journal Article |
| id | oai:localhost:123456789-173 |
| institution | DSPACE.FCHPT |
| language | English |
| publishDate | 2018 |
| publishDateRange | 2018 |
| publishDateSort | 2018 |
| record_format | dspace |
| spelling | oai:localhost:123456789-1732021-04-07T16:30:08Z A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis Simmons, Cameron 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. 2018-09-14T11:15:03Z 2017-07-05T05:57:30Z 2018-09-14T11:15:03Z 2006-06-16 2006-06-16 2006-06-16 2006-06-16 2006-06-16 2006-06-16 2006-06-16 2006-06-16 2006-10-15 Journal Article https://demo7.dspace.org/handle/123456789/173 English |
| spellingShingle | Simmons, Cameron 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 |
| url | https://demo7.dspace.org/handle/123456789/173 |
| work_keys_str_mv | AT simmonscameron apolymorphismintollinterleukin1receptordomaincontainingadaptorproteinisassociatedwithsusceptibilitytomeningealtuberculosis AT simmonscameron polymorphismintollinterleukin1receptordomaincontainingadaptorproteinisassociatedwithsusceptibilitytomeningealtuberculosis |