Abstract
BackgroundObtaining further knowledge regarding single nucleotide polymorphisms in the Toll-like receptor1 gene is of great importance to elucidate immunopathogenesis and management of tuberculosis.ResultsRs5743565 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)].ConclusionsRs5743565 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.MethodsWe 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.
Highlights
Tuberculosis (TB), caused by pathogenic Mycobacterium tuberculosis (MTB), remains a significant challenge to global public health [1]
Rs5743565 and rs5743557 in the Tolllike receptor 1 (TLR1) gene may contribute to decreased risk for tuberculosis susceptibility in a Western Chinese population
To provide evidence for the effect of TLR1 genetic polymorphisms on the development and progression of TB disease, we evaluated the association of TLR1 single nucleotide polymorphisms (SNPs) with predisposition to TB diseases, clinical phenotypes and ATDinduced adverse reactions in a prospective cohort of 1,121 adult participants from Western China
Summary
Tuberculosis (TB), caused by pathogenic Mycobacterium tuberculosis (MTB), remains a significant challenge to global public health [1]. Many research efforts have focused on identifying host genomic variants that are significantly associated with TB development as well as clinical phenotypes [7,8]. A large GWAS study from Sveinbjornsson G et al showed that HLA class II variants (rs557011, rs9271378 and rs9272785) contribute to the complex genetic risk of tuberculosis, possibly through reduced presentation of protective MTB antigens to T cells [9]. Considering the limited risk genetic variants and their finite significance on TB susceptibility, the exact host genetic elements that are involved in the biological process of TB infection remain to be understood. Obtaining further knowledge regarding single nucleotide polymorphisms in the Toll-like receptor gene is of great importance to elucidate immunopathogenesis and management of tuberculosis
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