A polymorphism in Toll-interleukin 1 receptor domain containing adaptor protein is associated with susceptibility to meningeal tuberculosis.
J Infect Dis
; 194(8): 1127-1134, 2006 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-16991088
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
3_ND
/
4_TD
Base de dados:
MEDLINE
Assunto principal:
Tuberculose Meníngea
/
Tuberculose Pulmonar
/
Receptores de Interleucina-1
/
Predisposição Genética para Doença
/
Receptores Toll-Like
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2006
Tipo de documento:
Article