Oncotarget

Research Papers:

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

Wu Peng, Hao Chen, Zhenzhen Zhao, Xuejiao Hu, Yi Zhou, Yingyu Li, Lian Yang, Xuemei Wang, Jiajia Song, Tangyuheng Liu, Qian Wu, Hao Bai, Xiaojun Lu, Jie Chen and Binwu Ying _

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Oncotarget. 2018; 9:1691-1704. https://doi.org/10.18632/oncotarget.23067

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Abstract

Wu Peng1,*, Hao Chen1,*, Zhenzhen Zhao1,*, Xuejiao Hu1, Yi Zhou1, Yingyu Li1, Lian Yang2, Xuemei Wang2, Jiajia Song1, Tangyuheng Liu1, Qian Wu1, Hao Bai1, Xiaojun Lu1, Jie Chen1 and Binwu Ying1

1Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, P.R. China

2Department of Laboratory Medicine, Chengdu Women and Children's Central Hospital, Chengdu 610091, P.R. China

*These authors contributed equally to this work

Correspondence to:

Binwu Ying, email: docbwy@126.com

Jie Chen, email: chenjie_wch@163.com

Keywords: tuberculosis; Toll-like receptor 1; single nucleotide polymorphisms; anti-TB drugs; adverse reactions

Received: August 21, 2017     Accepted: November 13, 2017     Published: December 08, 2017

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.


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