Association of <i>TLR4</i> gene polymorphism with tuberculosis susceptibility: an updated meta-analysis_West China Medical Journal

Authors：

PENG Wu , ZHAO Zhenzhen , SONG Jiajia , LIU Tangyuheng , ZHOU Wenjing , WU Lijuan , ZHUANG Jie , ZHOU Yi ,  CHEN Jie

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

Corresponding?author：

CHEN Jie, Email: chenjie_wch@163.com

Keywords：

Pulmonary tuberculosis; Toll-like receptor 4; Single nucleotide polymorphism; Meta-analysis

DOI：

10.7507/1002-0179.201907078

Video：

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Objective To explore the relationship between single nucleotide polymorphisms (SNPs) of the Toll-like receptor 4 (TLR4) gene and the risk of pulmonary tuberculosis (PTB) more comprehensively and objectively through meta-analysis.Methods We searched all available articles published before June 13th, 2019 in main Chinese and English databases systematically and comprehensively, including PubMed, Embase, China National Knowledge Infrastructure, Wanfang and CQVIP databases. The literature was screened according to the inclusion and exclusion criteria set in advance. In addition, the basic characteristics and data of the included literature were recorded according to a pre-made data collection form. Statistical analyses were performed using the Stata 15.0 software.Results A total of 17 eligible original articles were included in the study eventually. Furthermore, allele and genotype data of the 4 most widely studied SNPs (rs4986790, rs4986791, rs10759932, and rs11536889) in the TLR4 gene were extracted. And their allelic model, dominant model, recessive model, homozygous model, and heterozygous model were separately analyzed by meta-analysis. The results showed that the C allele of rs10759932 increased the risk of PTB [odd ratio (OR)=1.144, 95% confidence interval (CI) (1.043, 1.254), P=0.004]. Compared with the TT genotype, the CC+CT genotype and the CT genotype alone of rs10759932 also increased the risk of PTB [OR=1.218, 95%CI (1.084, 1.369), P=0.001; OR=1.227, 95%CI (1.085, 1.387), P=0.001]. Nevertheless, there was no statistical correlation between the other three SNPs (rs4986790, rs4986791 and rs11536889) and the susceptibility to PTB (P>0.05).Conclusion The allele model, dominant model (CC+CT vs. TT), and heterozygous model (CT vs. TT) of rs10759932 located on the TLR4 gene are closely related to the risk of PTB.

Citation： PENG Wu, ZHAO Zhenzhen, SONG Jiajia, LIU Tangyuheng, ZHOU Wenjing, WU Lijuan, ZHUANG Jie, ZHOU Yi, CHEN Jie. Association of TLR4 gene polymorphism with tuberculosis susceptibility: an updated meta-analysis. West China Medical Journal, 2019, 34(8): 870-877. doi: 10.7507/1002-0179.201907078 Copy

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2.	Jang AR, Kim G, Hong JJ, et al. Mycobacterium tuberculosis ESAT6 drives the activation and maturation of bone marrow-derived dendritic cells via TLR4-mediated signaling. Immune Netw, 2019, 19(2): e13.
3.	Jahantigh D, Salimi S, Alavi-Naini R, et al. Association between TLR4 and TLR9 gene polymorphisms with development of pulmonary tuberculosis in Zahedan, southeastern Iran. Sci World J, 2013, 2013: 534053.
4.	Yamamoto M, Sato S, Hemmi H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science, 2003, 301(5633): 640-643.
5.	Reiling N, Holscher C, Fehrenbach A, et al. Cutting edge: Toll-like receptor (TLR)2- and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis. J Immunol, 2002, 169(7): 3480-3484.
6.	Abel B, Thieblemont N, Quesniaux VJ, et al. Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice. J Immunol, 2002, 169(6): 3155-3162.
7.	Tian T, Jin SL, Dong JC, et al. Lack of association between Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms and tuberculosis susceptibility: a meta-analysis. Infect Genet Evol, 2013, 14: 156-160.
8.	Zhao LL, Liu KH, Kong XJ, et al. Association of polymorphisms in Toll-like receptors 4 and 9 with risk of pulmonary tuberculosis: a meta-analysis. Med Sci Monit, 2015, 21: 1097-1106.
9.	Schurz H, Daya M, M?ller M, et al. TLR1, 2, 4, 6 and 9 variants associated with tuberculosis susceptibility: a systematic review and meta-analysis. PLoS One, 2015, 10(10): e0139711.
10.	Ma X, Liu Y, Gowen BB, et al. Full-Exon resequencing reveals Toll-like receptor variants contribute to human susceptibility to tuberculosis disease. PLoS One, 2007, 2(12): e1318.
11.	Newport MJ, Allen A, Awomoyi AA, et al. The Toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia. Tuberculosis (Edinb), 2004, 84(6): 347-352.
12.	Fitness J, Floyd S, Warndorff DK, et al. Large-scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi. Am J Trop Med Hyg, 2004, 71(3): 341-349.
13.	Olesen R, Wejse C, Velez DR, et al. DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun, 2007, 8(6): 456-467.
14.	Rosas-Taraco AG, Revol A, Salinas-Carmona MC, et al. CD14 C(-159)T polymorphism is a risk factor for development of pulmonary tuberculosis. J Infect Dis, 2007, 196(11): 1698-1706.
15.	Najmi N, Kaur G, Sharma SK, et al. Human toll-like receptor 4 polymorphisms TLR4 asp299Gly and Thr399Ile influence susceptibility and severity of pulmonary tuberculosis in the Asian Indian population. Tissue Antigens, 2010, 76(2): 102-109.
16.	Selvaraj P, Harishankar M, Singh B, et al. Toll-like receptor and TIRAP gene polymorphisms in pulmonary tuberculosis patients of South India. Tuberculosis (Edinb), 2010, 90(5): 306-310.
17.	Sanchez D, Lefebvre C, Rioux J, et al. Evaluation of toll-like receptor and adaptor molecule polymorphisms for susceptibility to tuberculosis in a Colombian population. Int J Immunogenet, 2012, 39(3): 216-223.
18.	Zaki HY, Leung KH, Yiu WC, et al. Common polymorphisms in TLR4 gene associated with susceptibility to pulmonary tuberculosis in the Sudanese. Int J Tuberc Lung Dis, 2012, 16(7): 934-940.
19.	Torres-García D, Cruz-Lagunas A, García-Sancho FM, et al. Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population, 2013, 11: 220.
20.	李潔瓊, 謝蘭品, 董雅坤, 等. TLR4 基因多態性與中國漢族兒童結核病易感性的關聯研究. 山西醫科大學學報, 2014, 45(12): 1151-1158.
21.	Wu L, Hu Y, Li D, et al. Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population. BMC Med Genet, 2015, 16: 19.
22.	Salie M, Daya M, Lucas LA, et al. Association of toll-like receptors with susceptibility to tuberculosis suggests sex-specific effects of TLR8 polymorphisms. Infect Genet Evol, 2015, 34: 221-229.
23.	Jafari M, Nasiri MR, Sanaei R, et al. The NRAMP1, VDR, TNF-α, ICAM1, TLR2 and TLR4 gene polymorphisms in Iranian patients with pulmonary tuberculosis: a case-control study. Infect Genet Evol, 2016, 39: 92-98.
24.	Wang M, Xu G, Lü L, et al. Genetic polymorphisms of IL-17A, IL-17F, TLR4 and miR-146a in association with the risk of pulmonary tuberculosis. Sci Rep, 2016, 6: 28586.
25.	Wang XH, Ma AG, Han XX, et al. Relationship between Toll-like receptor 4 and type-2 diabetes mellitus complicated by tuberculosis. Int J Tuberc Lung Dis, 2017, 21(8): 910-915.

1. World Health Organization. Global tuberculosis report 2018. Geneva: World Health Organization. (2018-09-18)[2019-06-01]. https://www.who.int/tb/data/en/.
2. Jang AR, Kim G, Hong JJ, et al. Mycobacterium tuberculosis ESAT6 drives the activation and maturation of bone marrow-derived dendritic cells via TLR4-mediated signaling. Immune Netw, 2019, 19(2): e13.
3. Jahantigh D, Salimi S, Alavi-Naini R, et al. Association between TLR4 and TLR9 gene polymorphisms with development of pulmonary tuberculosis in Zahedan, southeastern Iran. Sci World J, 2013, 2013: 534053.
4. Yamamoto M, Sato S, Hemmi H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science, 2003, 301(5633): 640-643.
5. Reiling N, Holscher C, Fehrenbach A, et al. Cutting edge: Toll-like receptor (TLR)2- and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis. J Immunol, 2002, 169(7): 3480-3484.
6. Abel B, Thieblemont N, Quesniaux VJ, et al. Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice. J Immunol, 2002, 169(6): 3155-3162.
7. Tian T, Jin SL, Dong JC, et al. Lack of association between Toll-like receptor 4 gene Asp299Gly and Thr399Ile polymorphisms and tuberculosis susceptibility: a meta-analysis. Infect Genet Evol, 2013, 14: 156-160.
8. Zhao LL, Liu KH, Kong XJ, et al. Association of polymorphisms in Toll-like receptors 4 and 9 with risk of pulmonary tuberculosis: a meta-analysis. Med Sci Monit, 2015, 21: 1097-1106.
9. Schurz H, Daya M, M?ller M, et al. TLR1, 2, 4, 6 and 9 variants associated with tuberculosis susceptibility: a systematic review and meta-analysis. PLoS One, 2015, 10(10): e0139711.
10. Ma X, Liu Y, Gowen BB, et al. Full-Exon resequencing reveals Toll-like receptor variants contribute to human susceptibility to tuberculosis disease. PLoS One, 2007, 2(12): e1318.
11. Newport MJ, Allen A, Awomoyi AA, et al. The Toll-like receptor 4 Asp299Gly variant: no influence on LPS responsiveness or susceptibility to pulmonary tuberculosis in The Gambia. Tuberculosis (Edinb), 2004, 84(6): 347-352.
12. Fitness J, Floyd S, Warndorff DK, et al. Large-scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi. Am J Trop Med Hyg, 2004, 71(3): 341-349.
13. Olesen R, Wejse C, Velez DR, et al. DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun, 2007, 8(6): 456-467.
14. Rosas-Taraco AG, Revol A, Salinas-Carmona MC, et al. CD14 C(-159)T polymorphism is a risk factor for development of pulmonary tuberculosis. J Infect Dis, 2007, 196(11): 1698-1706.
15. Najmi N, Kaur G, Sharma SK, et al. Human toll-like receptor 4 polymorphisms TLR4 asp299Gly and Thr399Ile influence susceptibility and severity of pulmonary tuberculosis in the Asian Indian population. Tissue Antigens, 2010, 76(2): 102-109.
16. Selvaraj P, Harishankar M, Singh B, et al. Toll-like receptor and TIRAP gene polymorphisms in pulmonary tuberculosis patients of South India. Tuberculosis (Edinb), 2010, 90(5): 306-310.
17. Sanchez D, Lefebvre C, Rioux J, et al. Evaluation of toll-like receptor and adaptor molecule polymorphisms for susceptibility to tuberculosis in a Colombian population. Int J Immunogenet, 2012, 39(3): 216-223.
18. Zaki HY, Leung KH, Yiu WC, et al. Common polymorphisms in TLR4 gene associated with susceptibility to pulmonary tuberculosis in the Sudanese. Int J Tuberc Lung Dis, 2012, 16(7): 934-940.
19. Torres-García D, Cruz-Lagunas A, García-Sancho FM, et al. Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population, 2013, 11: 220.
20. 李潔瓊, 謝蘭品, 董雅坤, 等. TLR4 基因多態性與中國漢族兒童結核病易感性的關聯研究. 山西醫科大學學報, 2014, 45(12): 1151-1158.
21. Wu L, Hu Y, Li D, et al. Screening toll-like receptor markers to predict latent tuberculosis infection and subsequent tuberculosis disease in a Chinese population. BMC Med Genet, 2015, 16: 19.
22. Salie M, Daya M, Lucas LA, et al. Association of toll-like receptors with susceptibility to tuberculosis suggests sex-specific effects of TLR8 polymorphisms. Infect Genet Evol, 2015, 34: 221-229.
23. Jafari M, Nasiri MR, Sanaei R, et al. The NRAMP1, VDR, TNF-α, ICAM1, TLR2 and TLR4 gene polymorphisms in Iranian patients with pulmonary tuberculosis: a case-control study. Infect Genet Evol, 2016, 39: 92-98.
24. Wang M, Xu G, Lü L, et al. Genetic polymorphisms of IL-17A, IL-17F, TLR4 and miR-146a in association with the risk of pulmonary tuberculosis. Sci Rep, 2016, 6: 28586.
25. Wang XH, Ma AG, Han XX, et al. Relationship between Toll-like receptor 4 and type-2 diabetes mellitus complicated by tuberculosis. Int J Tuberc Lung Dis, 2017, 21(8): 910-915.

West China Medical Journal

Association of TLR4 gene polymorphism with tuberculosis susceptibility: an updated meta-analysis

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