Genome-wide association analysis of genetic susceptibility to hepatitis B virus co-infection in patients with pulmonary tuberculosis_West China Medical Journal

Authors：

YANG Xujie , JIAO Lin , BAI Hao ,  CHEN Jie , WU Qian , ZHAO Zhenzhen , MENG Zirui

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; Hepatitis B virus; Genome-wide association study; Single nucleotide polymorphism; Susceptibility genes

DOI：

10.7507/1002-0179.201907070

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the single locus mutation that related to hepatitis B virus (HBV) co-infection by means of genome-wide association study (GWAS) in Chinese Han patients with pulmonary tuberculosis (TB).Methods A total of 946 patients with pulmonary TB enrolled between March 2013 and March 2018 were genotyped by Illumina Human Omni Express gene chip. After quality control, 389 972 single nucleotide polymorphisms (SNPs) of 703 patients with single TB infection and 53 patients with TB-HBV co-infection were included in the follow-up association analysis.Results The SNP with the strongest statistical correlation signal was rs118122819 (P=2.923×10⁻¹², odds ratio=7.933) located on chromosome 8p23.1. Other potential susceptibility genes included CDH4 (rs73309833), MARCH1 (rs3797020), and DNER (rs13393112), etc. In addition, a strong linkage imbalance between rs118122819 and rs4840365 (D’=0.88, r²=0.76) was found, while rs4840365 was located in the MFHAS1 gene region.Conclusions This study provides evidence for the presence of susceptibility gene locus for HBV co-infection in pulmonary TB patients, and provides important clues for the mechanism research, disease prevention, and treatment of co-infection. But these associations must be replicated and validated in larger studies.

Citation： YANG Xujie, JIAO Lin, BAI Hao, CHEN Jie, WU Qian, ZHAO Zhenzhen, MENG Zirui. Genome-wide association analysis of genetic susceptibility to hepatitis B virus co-infection in patients with pulmonary tuberculosis. West China Medical Journal, 2019, 34(8): 885-889. doi: 10.7507/1002-0179.201907070 Copy

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14.	Cheng XM, Xia YC, Elisavet S, et al. Hepatitis B virus evades innate immunity of hepatocytes but activates macrophages during infection. Hepatology, 2017, 66(6): 1779-1793.
15.	Lei C, Tian L, Long W, et al. The association between three IL-6 polymorphisms and HBV-related liver diseases: a meta-analysis. Int J Clin Exp Med, 2015, 8(10): 17036-17045.
16.	Shen P, Li Q, Ma J, et al. IRAK-M alters the polarity of macrophages to facilitate the survival of Mycobacterium tuberculosis. BMC Microbiol, 2017, 17(1): 185.
17.	O'Halloran S, O’Leary A, Kuijper T, et al. MyD88 acts as an adaptor protein for inflammatory signalling induced by amyloid-beta in macrophages. Immunol Lett, 2014, 162(1 Pt A): 109-118.
18.	Wilson KR, Liu H, Healey G, et al. MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway. PLoS One, 2018, 13(7): e0200540.
19.	Xie L, Dai H, Li M, et al. MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K-AKT-β-catenin pathways. J Cell Mol Med, 2019, 23(5): 3386-3401.
20.	Wang HW, Gao HL, Wei XX, et al. Up-regulation of IL-12 expression in patients with chronic hepatitis B is mediated by the PI3K/Akt pathway. Mol Cell Biochem, 2015, 407(1/2): 135-142.
21.	Ballester-López C, Conlon TM, Ertüz Z, et al. The Notch ligand DNER regulates macrophage IFNγ release in chronic obstructive pulmonary disease. EBioMedicine, 2019, 43: 562-575.
22.	Liang Y, Luo H, Zhang H, et al. Oncogene Delta/Notch-Like EGF-related receptor promotes cell proliferation, invasion, and migration in hepatocellular carcinoma and predicts a poor prognosis. Cancer Biother Radiopharm, 2018, 33(9): 380-386.
23.	Omae Y, Toyo-Oka L, Yanai H, et al. Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis. J Hum Genet, 2017, 62(12): 1015-1022.

1. 中华医学会肝病学分会联合中华医学会感染病学分会. 慢性乙型肝炎防治指南: 2015 年更新. 中华肝脏病杂志, 2015, 3(12): 888-905.
2. 王黎霞, 成诗明, 陈明亭, 等. 2010 年全国第五次结核病流行病学抽样调查报告. 中国防痨杂志, 2012, 34(8): 485-508.
3. 张贵贤, 张艳丽, 李木松, 等. 肺结核合并乙肝病毒感染的临床现状与分析. 医药卫生, 2018, 8(2): 45-48.
4. Trépo C, Chan HL, Lok A, et al. Hepatitis B virus infection. Lancet, 2014, 384: 2053-2063.
5. McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology, 2009, 49(5 Suppl): S45-S55.
6. Simonds B. Tuberculosis in twins: a report for the Prophit Committee of the Royal College of Physicians. London: Pitman Medical Publishing, 1963.
7. He YL, Zhao YR, Zhang SL, et al. Host susceptibility to persistent hepatitis B virus infection. World J Gastroenterol, 2006, 12(30): 4788-4793.
8. Zheng R, Li Z, He F, et al. Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese. Nat Commun, 2018, 9(1): 4072.
9. Shi H, He H, Ojha SC, et al. Association of STAT3 and STAT4 polymorphisms with susceptibility to chronic hepatitis B virus infection and risk of hepatocellular carcinoma: a meta-analysis. Biosci Rep, 2019, 39(6): 1-15.
10. 王贵强, 王福生, 成军, 等. 慢性乙型肝炎防治指南: 2015 年更新版. 临床肝胆病杂志, 2015, 31(12): 1941-1960.
11. 中华人民共和国国家卫生和计划生育委员会. 肺结核诊断标准: WS 288－2017, 2017.
12. Zumla A, Raviglione M, Hafner R, et al. Tuberculosis. N Engl J Med, 2013, 368(8): 745-755.
13. Ng AC, Eisenberg JM, Heath RJ, et al. Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity. Proc Natl Acad Sci USA, 2011, 108(Suppl 1): 4631-4638.
14. Cheng XM, Xia YC, Elisavet S, et al. Hepatitis B virus evades innate immunity of hepatocytes but activates macrophages during infection. Hepatology, 2017, 66(6): 1779-1793.
15. Lei C, Tian L, Long W, et al. The association between three IL-6 polymorphisms and HBV-related liver diseases: a meta-analysis. Int J Clin Exp Med, 2015, 8(10): 17036-17045.
16. Shen P, Li Q, Ma J, et al. IRAK-M alters the polarity of macrophages to facilitate the survival of Mycobacterium tuberculosis. BMC Microbiol, 2017, 17(1): 185.
17. O'Halloran S, O’Leary A, Kuijper T, et al. MyD88 acts as an adaptor protein for inflammatory signalling induced by amyloid-beta in macrophages. Immunol Lett, 2014, 162(1 Pt A): 109-118.
18. Wilson KR, Liu H, Healey G, et al. MARCH1-mediated ubiquitination of MHC II impacts the MHC I antigen presentation pathway. PLoS One, 2018, 13(7): e0200540.
19. Xie L, Dai H, Li M, et al. MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K-AKT-β-catenin pathways. J Cell Mol Med, 2019, 23(5): 3386-3401.
20. Wang HW, Gao HL, Wei XX, et al. Up-regulation of IL-12 expression in patients with chronic hepatitis B is mediated by the PI3K/Akt pathway. Mol Cell Biochem, 2015, 407(1/2): 135-142.
21. Ballester-López C, Conlon TM, Ertüz Z, et al. The Notch ligand DNER regulates macrophage IFNγ release in chronic obstructive pulmonary disease. EBioMedicine, 2019, 43: 562-575.
22. Liang Y, Luo H, Zhang H, et al. Oncogene Delta/Notch-Like EGF-related receptor promotes cell proliferation, invasion, and migration in hepatocellular carcinoma and predicts a poor prognosis. Cancer Biother Radiopharm, 2018, 33(9): 380-386.
23. Omae Y, Toyo-Oka L, Yanai H, et al. Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis. J Hum Genet, 2017, 62(12): 1015-1022.

West China Medical Journal

Genome-wide association analysis of genetic susceptibility to hepatitis B virus co-infection in patients with pulmonary tuberculosis

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