TLR1 polymorphisms are significantly associated with the occurrence, presentation and drug-adverse reactions of tuberculosis in Western Chinese adults

Abstract

Background: Obtaining further knowledge regarding single nucleotide polymorphisms in the Toll-like receptor1 gene is of great importance to elucidate immunopathogenesis and management of tuberculosis.

Results: Rs5743565 and rs5743557 were significantly associated with reduced predisposition to TB regarding the mutant allele in additive and dominant models with odds ratios (ORs) ranging from 0.61 to 0.83. There was increased tuberculosis risk associated with the haplotype CAG (rs4833095/rs76600635/rs5743596) [OR (95% CI) = 1.33 (1.07–1.65)] and with haplotype GG (rs56357984/rs5743557) [OR = 1.21 (1.02–1.43)]. The erythrocyte and hemoglobin levels were significantly higher in TB patients with the rs5743557 GG genotype than for AA and/or AG genotype carriers (p = 0.006 and 0.020, respectively). The occurrence rates of chronic kidney damage and hepatotoxicity were 21.56% and 10.32%, respectively. Rs5743565 seemed to pose a higher risk of anti-TB-induced hepatotoxicity under the dominant model [OR = 2.17 (1.17–4.05)], and rs76600635 GG/AG genotypes were clearly correlated with the development of thrombocytopenia [OR = 2.98 (1.26–7.09)].

Conclusions: Rs5743565 and rs5743557 in the TLR1 gene may contribute to decreased risk for tuberculosis susceptibility in a Western Chinese population. Rs5743565 and rs76600635 are potential risk factors for adverse reactions to anti-TB drugs.

Methods: We enrolled 646 tuberculosis patients and 475 healthy controls from West China. Six single nucleotide polymorphisms in Toll-like receptor1 gene were genotyped in every individual and were analyzed for their association with tuberculosis susceptibility and clinical presentation. The prospective follow-up was performed to determine whether these single nucleotide polymorphisms are associated with adverse reactions to anti-tuberculosis drugs.