| סיכום: | <p style="text-align:justify;"> <b>Background: </b>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)<br/> <b>Methods: </b>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<br/> <b>Results: </b>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<br/> <b>Conclusions: </b>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 </p>
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