Association of the variant rs5743557 with susceptibility to tuberculosis.

BACKGROUND

Toll-like receptor 1 (TLR1) and TLR6 play important roles in the innate immune response against (M.TB) via interactions with TIR domain-containing adaptor protein (TIRAP) and myeloid differentiation primary response 88 (MYD88). The aim of this study was to investigate the relationship of and polymorphisms with susceptibility to latent tuberculosis infection (LTBI) and tuberculosis (TB).

METHODS

In total, 204 uninfected healthy controls (HC), 201 individuals with LTBI and 209 TB patients were enrolled. Two interferon-γ release assays were used to differentiate individuals with LTBI from uninfected controls. TagSNPs of the four genes were genotyped by the SNPscan Kit. The Haploview 4.2 and SHEsis software packages were combined to perform linkage disequilibrium (LD) and haplotype analyses. Multifactor dimensionality reduction (MDR) software was used to investigate gene-gene interaction. The Stata 12.0 software was used to perform meta-analysis of the relationship between rs5743557 and TB susceptibility.

RESULTS

The AA genotype of rs5743557 was associated with reduced TB risk (P=0.006) and the AA/GA genotypes of rs5743604 were associated with increased TB risk (P=0.017) when the LTBI group was compared with the TB group. The frequency of haplotype rs4833095-rs5743604 CG was significantly higher in the LTBI group than in the TB group (P=0.019877). However, only the relationship between rs5743557 and TB susceptibility remained significant after 1000-fold permutation testing (P=0.023). The meta-analysis suggested that rs5743557_A was associated with decreased TB risk in the Chinese adult population (P<0.001, OR 0.80, 95% CI: 0.72-0.88). No significant gene-gene interactions were found.

CONCLUSIONS

The results of our study suggest that the tagSNP rs5743557 of is associated with the risk of TB.