Thuong, N. T. et al. A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis. Genes Immun. 8, 422-428

Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Genes and Immunity (Impact Factor: 2.91). 08/2007; 8(5):422-8. DOI: 10.1038/sj.gene.6364405
Source: PubMed


Tuberculous meningitis (TBM) results from the haematogenous dissemination of Mycobacterium tuberculosis from the lung to the brain. Dissemination is believed to occur early during infection, before the development of adaptive immunity. Toll-like receptor 2 (TLR2) mediates recognition of M. tuberculosis and initiates the innate immune response to infection. We hypothesized that polymorphisms in the TLR2 gene influence bacterial dissemination and the development of TBM. A case-control study was designed to test the hypothesis. Cases of bacteriologically confirmed pulmonary tuberculosis (TB) (n=183) and TBM (n=175), and cord blood controls (n=389) were enrolled in Vietnam. TLR2 genotype 597CC was associated with susceptibility to TB (odds ratio (OR)=2.22, 95% confidence interval (CI): 1.23-3.99). The association was found with meningeal rather than pulmonary TB (TBM vs control, OR=3.26, 95% CI: 1.72-6.18), and was strongest when miliary TB was found on chest radiography (controls vs TBM with miliary TB, OR=5.28, 95% CI: 2.20-12.65). Furthermore, the association increased with the severity of neurologic symptoms (grade I TBM, OR=1.93, 95% CI: 0.54-6.92; grade II, OR=3.32, 95% CI: 0.84-13.2; and grade III, OR=5.70, 95% CI: 1.81-18.0). These results demonstrate a strong association of TLR2 SNP T597C with the development of TBM and miliary TB and indicate that TLR2 influences the dissemination of M. tuberculosis.

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Available from: Nguyen Trong Hieu, May 28, 2014
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    • "Single nucleotide polymorphisms (SNPs) in immune response genes may be associated with susceptibility to diseases [7] [8]. SNPs in immune response genes may also influence susceptibility to infection or result in variation of individual response to pathogenic agents [9]. "
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    • "For example, individuals with TLR2 Arg753Gln single nucleotide polymorphisms (SNPs) are found to be more susceptible to TB compared to healthy controls of a Turkish cohort [53]. Several other SNPs such as TLR2 Arg677Trp, TLR2 597CC, and TLR2 T597C also show an association with susceptibility to TB in different cohorts [54–56] indicating that the TLR2 polymorphisms influence the susceptibility to Mtb infection. "
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    11/2013; 2013(5):179174. DOI:10.1155/2013/179174
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    • "Several studies have explored the association between PTB susceptibility and SNPs of TLR2 gene, among which G2258A and T597C were the two most widely discussed SNPs. Lorenz et al. [15] found that the mutation of G2258A could decrease the response of macrophages to bacterial peptides, while Thuong et al. [16] reported that T597C might result in an attenuated early innate immune response to infection with M. tuberculosis. "
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