A Polymorphism in Toll-Interleukin 1 Receptor Domain Containing Adaptor Protein Is Associated with Susceptibility to Meningeal Tuberculosis

BackgroundAlthough 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) MethodsWe 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 ResultsThe 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