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TLR1 Polymorphisms Associated with Susceptibility to Latent Tuberculosis Infection and Active Tuberculosis
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A4306 - TLR1 Polymorphisms Associated with Susceptibility to Latent Tuberculosis Infection and Active Tuberculosis
Author Block: M. M. Zhang, J. He; Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China, Chengdu, China.
RATIONALE: Toll-like receptor 1 (TLR1) and TLR6, play an important role in the innate immune response against Mycobacterium tuberculosis (M.TB) via interacting with TIR domain-containing adaptor protein (TIRAP) and myeloid differentiation primary response 88 (MYD88) protein. The aim of this study was to investigate the relationship between polymorphisms of four genes (TLR1, TLR6, MYD88 and TIRAP) and susceptibility to latent tuberculosis infection (LTBI) and tuberculosis (TB). METHODS: In total, 204 uninfected healthy controls (HC), 201 LTBI individuals and 209 TB patients were enrolled. TagSNPs of the four genes were genotyped by the SNPscanTM Kit. Haploview 4.2 and online SHEsis were combined to perform linkage disequilibrium (LD) and haplotype analysis. Multifactor dimensionality reduction (MDR) software was adapted to investigate gene-gene interaction. RESULTS: After adjusting for confounding factors, several significant associations were found in tagSNPs of TLR1. Genotype TT and TC of rs4833095 were associated with reduced M.TB infection (p=0.007). Genotype AA of rs5743596 protected against LTBI progression to TB (p=0.036). Genotype AA rs5743557 increased M.TB infection but decreased risk of TB and LTBI progression to TB (p=0.012, OR 1.99, p=0.048, OR 0.60 and p=0.006, OR 0.451, respectively). Genotype GA and AA of rs5743604 protected against TB infection but increased the risk of TB developing from LTBI (p=0.034, OR 0.618 and p=0.017, OR 1.78). The TLR1 haplotype rs4833095-rs5743604 CG was significantly higher in the LTBI group (p=0.0198) compared with the TB group. No significant associations were found in other three genes and no significant gene-gene interaction was detected. CONCLUSIONS: Our study suggests that SNPs of TLR1 gene were associated with risk of TB infection and LTBI progression to TB for the first time.
Author Block: M. M. Zhang, J. He; Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China, Chengdu, China.
RATIONALE: Toll-like receptor 1 (TLR1) and TLR6, play an important role in the innate immune response against Mycobacterium tuberculosis (M.TB) via interacting with TIR domain-containing adaptor protein (TIRAP) and myeloid differentiation primary response 88 (MYD88) protein. The aim of this study was to investigate the relationship between polymorphisms of four genes (TLR1, TLR6, MYD88 and TIRAP) and susceptibility to latent tuberculosis infection (LTBI) and tuberculosis (TB). METHODS: In total, 204 uninfected healthy controls (HC), 201 LTBI individuals and 209 TB patients were enrolled. TagSNPs of the four genes were genotyped by the SNPscanTM Kit. Haploview 4.2 and online SHEsis were combined to perform linkage disequilibrium (LD) and haplotype analysis. Multifactor dimensionality reduction (MDR) software was adapted to investigate gene-gene interaction. RESULTS: After adjusting for confounding factors, several significant associations were found in tagSNPs of TLR1. Genotype TT and TC of rs4833095 were associated with reduced M.TB infection (p=0.007). Genotype AA of rs5743596 protected against LTBI progression to TB (p=0.036). Genotype AA rs5743557 increased M.TB infection but decreased risk of TB and LTBI progression to TB (p=0.012, OR 1.99, p=0.048, OR 0.60 and p=0.006, OR 0.451, respectively). Genotype GA and AA of rs5743604 protected against TB infection but increased the risk of TB developing from LTBI (p=0.034, OR 0.618 and p=0.017, OR 1.78). The TLR1 haplotype rs4833095-rs5743604 CG was significantly higher in the LTBI group (p=0.0198) compared with the TB group. No significant associations were found in other three genes and no significant gene-gene interaction was detected. CONCLUSIONS: Our study suggests that SNPs of TLR1 gene were associated with risk of TB infection and LTBI progression to TB for the first time.
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