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Background  We investigated whether polymorphisms in the toll-like receptor genes or gene–gene interactions are associated with susceptibility to latent tuberculosis infection (LTBI) or subsequent pulmonary tuberculosis (PTB) in a Chinese population.    Methods  Two matched case–control studies were undertaken. Previously reported polymorphisms in the toll-like receptors (TLRs) were compared between 422 healthy controls (HC) and 205 LTBI patients and between 205 LTBI patients and 109 PTB patients, to assess whether these polymorphisms and their interactions are associated with LTBI or PTB. A PCR-based restriction fragment length polymorphism analysis was used to detect genetic polymorphisms in the  TLR  genes. Nonparametric multifactor dimensionality reduction (MDR) was used to analyze the effects of interactions between complex disease genes and other genes or environmental factors.    Results  Sixteen markers in  TLR1 ,  TLR2 ,  TLR4 ,  TLR6 ,  TLR8 ,  TLR9 , and  TIRAP  were detected. In  TLR2 , the frequencies of the CC genotype (OR = 2.262; 95% CI: 1.433–3.570) and C allele (OR = 1.566; 95% CI: 1.223–1.900) in single-nucleotide polymorphism (SNP) rs3804100 were significantly higher in the LTBI group than in the HC group, whereas the GA genotype of SNP rs5743708 was associated with PTB (OR = 6.087; 95% CI: 1.687–21.968). The frequencies of the GG genotype of SNP rs7873784 in  TLR4  (OR = 2.136; 95% CI: 1.312–3.478) and the CC genotype of rs3764879 in  TLR8  (OR = 1.982; 95% CI: 1.292-3.042) were also significantly higher in the PTB group than in the HC group. The TC genotype frequency of SNP rs5743836 in  TLR9  was significantly higher in the LTBI group than in the HC group (OR = 1.664; 95% CI: 1.201–2.306). An MDR analysis of gene–gene and gene–environment interactions identified three SNPs (rs10759932, rs7873784, and rs10759931) that predicted LTBI with 84% accuracy ( p  = 0.0004) and three SNPs (rs3804100, rs1898830, and rs10759931) that predicted PTB with 80% accuracy ( p  = 0.0001).    Conclusions  Our results suggest that genetic variation in TLR2, 4, 8 and 9, implicating TLR-related pathways affecting the innate immunity response, modulate LTBI and PTB susceptibility in Chinese.    Electronic supplementary material  The online version of this article (doi:10.1186/s12881-015-0166-1) contains supplementary material, which is available to authorized users.

Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population