Skip to main content
Top
Published in: BMC Infectious Diseases 1/2018

Open Access 01-12-2018 | Research article

Correlation between polymorphisms in toll-like receptor genes and the activity of hepatitis B virus among treatment-naïve patients: a case-control study in a Han Chinese population

Authors: Yong Lin, Zheng-Xiang Gao, Xu Shen, Mei-Jun Chen, Yan-Ting Li, Shu-Lian Li, Hui-Ling Lin, Qi-Feng Zhao, Fan Liu, Jian-Jun Niu

Published in: BMC Infectious Diseases | Issue 1/2018

Login to get access

Abstract

Background

Because of the high prevalence and absence of cure for infection, chronic hepatitis B virus (HBV) infection has been acknowledged as a pressing public health issue. Toll-like receptors (TLRs) activate the human innate immune system and the polymorphisms in TLRs may alter their function. The present study aimed to investigate the association between TLR polymorphisms and disease progression of chronic HBV infection.

Methods

During the study period, 211 treatment-naïve patients with chronic HBV infection were recruited, and blood samples were collected from each individual. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was employed to genotype the selected TLR polymorphisms after human genome extraction. In addition, HbsAg, TNF-α, and IL-6 levels were quantified using enzyme linked immunosorbent assay (ELISA). Statistical analyses were conducted to investigate the association between TLR polymorphisms and hepatitis activity, liver function parameters, HbsAg level, and cytokine level.

Results

We did not observe any mutations in rs4986790, rs4986791, and rs5743708 among all study subjects. A logistic regression revealed that mutations in rs3804099 and rs4696480 were associated with milder hepatitis activity. Consistent with the logistic regression, improved liver function parameters and reduced level of both HbsAg and cytokines were also correlated with the mutant carriers of rs3804099 and rs4696480.

Conclusions

TLR mutations were significantly associated with milder hepatitis activity among patients with chronic HBV infection. Therefore, we conclude that the activation of TLR pathways may further intensify the inflammation of hepatocytes, and leads to progression of disease.
Literature
1.
go back to reference Wang Q, Xu Y, Zhou W, Zhong L, Wen Z, Yu H, et al. The viral oncoprotein HBx of hepatitis B virus promotes the growth of hepatocellular carcinoma through cooperating with the cellular oncoprotein RMP. Int J Biol Sci. 2014;10(10):1181–92.CrossRefPubMedPubMedCentral Wang Q, Xu Y, Zhou W, Zhong L, Wen Z, Yu H, et al. The viral oncoprotein HBx of hepatitis B virus promotes the growth of hepatocellular carcinoma through cooperating with the cellular oncoprotein RMP. Int J Biol Sci. 2014;10(10):1181–92.CrossRefPubMedPubMedCentral
3.
4.
go back to reference Bartholomeusz A, Tehan BG, Chalmers DK. Comparisons of the HBV and HIV polymerase, and antiviral resistance mutations. Antivir Ther. 2004;9(2):149–60.PubMed Bartholomeusz A, Tehan BG, Chalmers DK. Comparisons of the HBV and HIV polymerase, and antiviral resistance mutations. Antivir Ther. 2004;9(2):149–60.PubMed
5.
go back to reference Baxa DM, Thekdi AD, Golembieski A, Krishnan PV, Sharif O, Kizy A, et al. Evaluation of anti-HBV drug resistant mutations among patients with acute symptomatic hepatitis B in the United States. J Hepatol. 2013;58(2):212–6.CrossRefPubMed Baxa DM, Thekdi AD, Golembieski A, Krishnan PV, Sharif O, Kizy A, et al. Evaluation of anti-HBV drug resistant mutations among patients with acute symptomatic hepatitis B in the United States. J Hepatol. 2013;58(2):212–6.CrossRefPubMed
6.
go back to reference GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;385(9963):117–71.CrossRef GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;385(9963):117–71.CrossRef
7.
go back to reference Busch K, Thimme R. Natural history of chronic hepatitis B virus infection. Med Microbiol Immunol. 2015;204(1):5–10.CrossRefPubMed Busch K, Thimme R. Natural history of chronic hepatitis B virus infection. Med Microbiol Immunol. 2015;204(1):5–10.CrossRefPubMed
8.
go back to reference Lauret E, González-Diéguez ML, Rodríguez M, Rodríguez M, González M, Melón S, et al. Long-term outcome in Caucasian patients with chronic hepatitis B virus infection after HBsAg seroclearance. Liver Int. 2015;35(1):140–7.CrossRefPubMed Lauret E, González-Diéguez ML, Rodríguez M, Rodríguez M, González M, Melón S, et al. Long-term outcome in Caucasian patients with chronic hepatitis B virus infection after HBsAg seroclearance. Liver Int. 2015;35(1):140–7.CrossRefPubMed
9.
go back to reference Milosevic I, Delic D, Lazarevic I, Pavlovic IP, Korac M, Bojovic K, et al. The significance of hepatitis B virus (HBV) genotypes for the disease and treatment outcome among patients with chronic hepatitis B in Serbia. J Clin Virol 2013; 58(1):54-8. Milosevic I, Delic D, Lazarevic I, Pavlovic IP, Korac M, Bojovic K, et al. The significance of hepatitis B virus (HBV) genotypes for the disease and treatment outcome among patients with chronic hepatitis B in Serbia. J Clin Virol 2013; 58(1):54-8.
10.
go back to reference Roh YS, Seki E. Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis. J Gastroenterol Hepatol. 2013;28(Suppl 1):38–42.CrossRefPubMedPubMedCentral Roh YS, Seki E. Toll-like receptors in alcoholic liver disease, non-alcoholic steatohepatitis and carcinogenesis. J Gastroenterol Hepatol. 2013;28(Suppl 1):38–42.CrossRefPubMedPubMedCentral
11.
go back to reference Chen Y, Sun R. Toll-like receptors in acute liver injury and regeneration. Int Immunopharmacol. 2011;11(10):1433–41.CrossRefPubMed Chen Y, Sun R. Toll-like receptors in acute liver injury and regeneration. Int Immunopharmacol. 2011;11(10):1433–41.CrossRefPubMed
12.
go back to reference The French METAVIR Cooperative Study Group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology. 1994;20(1):15–20.CrossRef The French METAVIR Cooperative Study Group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology. 1994;20(1):15–20.CrossRef
13.
go back to reference Hang J, Zhou W, Zhang H, Sun B, Dai H, Su L, et al. TLR4 Asp299Gly and Thr399Ile polymorphisms are very rare in the Chinese population. J Endotoxin Res. 2004;10(4):238–40.CrossRefPubMed Hang J, Zhou W, Zhang H, Sun B, Dai H, Su L, et al. TLR4 Asp299Gly and Thr399Ile polymorphisms are very rare in the Chinese population. J Endotoxin Res. 2004;10(4):238–40.CrossRefPubMed
14.
go back to reference Tahara T, Arisawa T, Shibata T, Hirata I, Nakano H. Absence of common polymorphisms of toll like receptor 4 (TLR4): Asp299Gly, Thr399Ile in patients with Gastroduodenal diseases in Japan. J Clin Biochem Nutr. 2007;40(1):62–5.CrossRefPubMed Tahara T, Arisawa T, Shibata T, Hirata I, Nakano H. Absence of common polymorphisms of toll like receptor 4 (TLR4): Asp299Gly, Thr399Ile in patients with Gastroduodenal diseases in Japan. J Clin Biochem Nutr. 2007;40(1):62–5.CrossRefPubMed
15.
go back to reference Zhang X, Ma Z, Liu H, Liu J, Meng Z, Broering R, et al. Role of toll-like receptor 2 in the immune response against hepadnaviral infection. J Hepatol. 2012;57(3):522–8.CrossRefPubMed Zhang X, Ma Z, Liu H, Liu J, Meng Z, Broering R, et al. Role of toll-like receptor 2 in the immune response against hepadnaviral infection. J Hepatol. 2012;57(3):522–8.CrossRefPubMed
16.
go back to reference Isogawa M, Robek MD, Furuichi Y, Chisari FV. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol. 2005;79(11):7269–72.CrossRefPubMedPubMedCentral Isogawa M, Robek MD, Furuichi Y, Chisari FV. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol. 2005;79(11):7269–72.CrossRefPubMedPubMedCentral
17.
go back to reference Wu J, Meng Z, Jiang M, Zhang E, Trippler M, Broering R, et al. Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific. Immunology. 2010;129(3):363–74.CrossRefPubMedPubMedCentral Wu J, Meng Z, Jiang M, Zhang E, Trippler M, Broering R, et al. Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific. Immunology. 2010;129(3):363–74.CrossRefPubMedPubMedCentral
18.
go back to reference Moradzadeh M, Tayebi S, Poustchi H, Sayehmiri K, Shahnazari P, Naderi E, et al. The possible role of TLR2 in chronic hepatitis B patients with Precore mutation. Adv Virol. 2013;2013:780319.CrossRefPubMedPubMedCentral Moradzadeh M, Tayebi S, Poustchi H, Sayehmiri K, Shahnazari P, Naderi E, et al. The possible role of TLR2 in chronic hepatitis B patients with Precore mutation. Adv Virol. 2013;2013:780319.CrossRefPubMedPubMedCentral
19.
go back to reference Kim YJ, Cho HC, Choi MS, Lee JH, Koh KC, Yoo BC, et al. The change of the quantitative HBsAg level during the natural course of chronic hepatitis B. Liver Int. 2011;31(6):817–23.CrossRefPubMed Kim YJ, Cho HC, Choi MS, Lee JH, Koh KC, Yoo BC, et al. The change of the quantitative HBsAg level during the natural course of chronic hepatitis B. Liver Int. 2011;31(6):817–23.CrossRefPubMed
20.
go back to reference Visvanathan K, Skinner NA, Thompson AJ, Riordan SM, Sozzi V, Edwards R, et al. Regulation of toll-like receptor-2 expression in chronic hepatitis B by the precore protein. Hepatology. 2007;45(1):102–10.CrossRefPubMed Visvanathan K, Skinner NA, Thompson AJ, Riordan SM, Sozzi V, Edwards R, et al. Regulation of toll-like receptor-2 expression in chronic hepatitis B by the precore protein. Hepatology. 2007;45(1):102–10.CrossRefPubMed
Metadata
Title
Correlation between polymorphisms in toll-like receptor genes and the activity of hepatitis B virus among treatment-naïve patients: a case-control study in a Han Chinese population
Authors
Yong Lin
Zheng-Xiang Gao
Xu Shen
Mei-Jun Chen
Yan-Ting Li
Shu-Lian Li
Hui-Ling Lin
Qi-Feng Zhao
Fan Liu
Jian-Jun Niu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2018
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-018-2943-x

Other articles of this Issue 1/2018

BMC Infectious Diseases 1/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.