Human genetic susceptibility to tuberculous meningitis in Vietnamese population
Thuong NTT., Dunstan S.
A case-control study of TLR2 candidate found that genotype 597CC was associated with susceptibility to tuberculous meningitis (TBM) (OR = 3.26)1). SNP C558T on TIRAP was found to be associated with increased susceptibility to TBM in this same Vietnamese cohort2) (OR= 3.02). The co-inheritance of TLR2 SNP T597C and TIRAP SNP C558T increases susceptibility to TBM (OR = 5.4). The interaction between polymorphisms on TLR2 and TIRAP in TB patients and M. tuberculosis strains shows that individuals with the C allele of TLR2 T597C are more likely to have TBM caused by the Beijing genotype (OR=1.91) than other individuals. TBM patients with CC genotype of TLR2 T597C have higher risk of disease caused by the Beijing genotype (OR=4.48). This provides evidence that M.tuberculosis genotype influences clinical disease phenotype3). A genome-wide case-control association study of 250,000 SNPs indicated that there are SNP marker profiles which are specifically associated with the susceptibility to, or protection from, clinical phenotypes of TB (data not yet published). Microarrays were used to determine gene expression profiles of over 38,500 genes from ex-vivo M.tuberculosis stimulated macrophages isolated from latent (LTB), PTB and TBM. These results suggest that distinct macrophage responses are associated with different clinical forms of tuberculosis and that the innate immune response may regulate clinical outcomes4). Overall, the work presented in these studies contributes to the current knowledge of the genetic basis of TB, and more specifically of TBM, and provides novel insights into the molecular pathogenesis of TB.