Variants of Toll-like receptor 6 associated with tuberculosis susceptibility in the Chinese Tibetan population

Background: Our investigation attempted to understand the role of innate immunity related genes played in tuberculosis. The relationship between single-nucleotide polymorphisms (SNPs) of three innate immunity-related genes (TLR6, MyD88, and TIRAP) and tuberculosis (TB) risk in two Chinese populations were explored.

Methods: Totally 1185 Chinese Han, consisting of 580 active TB cases and 605 healthy controls (HCs), and 1216 Chinese Tibetan individuals including 613 TB patients and 603 HCs were enrolled to conduct two case-control studies. TagSNPs of the three genes were selected based on the HapMap database and genotyped by the SNPscan™ Kit. Haploview software 4.2 was applied to perform linkage disequilibrium (LD) analysis and online software SHEsis was used to discover significant haplotype block. RegulomeDB and HaploReg were applied to predict potential functional SNPs of the three genes.

Results: The results showed that minor alleles of rs5743808 and rs5743827 of TLR6 were related with increased TB risk (p = 0.001, OR 95%CI = 1.51 (1.18-1.95) and p = 0.002, OR 95%CI = 1.42 (1.14-1.77)), and significant association was also observed between rs5743827 and TB risk in male subgroup (p = 0.003, OR 95%CI = 1.67 (1.91-2.35)) in the Tibetan population. For the Tibetan population, frequency of haplotype ACGT of rs1039559-rs3775073-rs5743808-rs5743827 of TLR6 was significantly higher in the TB group (p = 0.0008), while haplotype ATAC was significantly higher in the control group (p = 0.0002). The above associations remained after permutation and Bonferroni correction. No significant association was found in the Han population. Probable functions of tagSNPs of TLR6 and some other linked variants were discovered after bioinformatic analysis.

Conclusions: This study suggested that variants of TLR6 might be associated with TB risk in the Tibetan population, while not in the Han population. The difference between Chinese Han and Tibetan people will provide better understanding of tuberculosis.