title: IL6 gene allele-specific C/EBPα-binding activity affects the development of HBV infection through modulation of Th17/Treg balance.
abstract: Interleukin-6 (IL-6) has an important role in the pathogenesis of chronic viral hepatitis and related liver diseases. Although host genetics associated with the response to anti-viral treatment have been reported, little is known about the relationship between IL6 genetic polymorphisms and the outcome of hepatitis B virus (HBV) infection. In this study, we determined the genotype distribution of rs1800796 polymorphism in healthy controls and cases including chronic HBV (CHB), hepatitis C virus and HIV infection. The rs1800796 was found to be associated with clinical outcome of CHB in experimental and validation cohort. The rs1800796C allele has twofold higher promoter activity than G allele. Consistently, CD14(+) monocytes from subjects carrying the rs1800796C allele produced more IL-6 in response to in vitro HBV core antigen stimulation than those carrying G allele. Moreover, CHB patients carrying rs1800796C allele have significantly higher T-helper 17 (Th17) and regulatory T cell (Treg) ratio. Finally, a transcription factor C/EBPα binds in higher affinity to rs1800796C allele than to G allele. These results suggest that genetic predisposition to higher IL-6 production is associated with increased risk to HBV infection and hepatic inflammation, which might be due to C/EBPα-mediated regulatory effect on Th17 and Treg responses. Appropriate manipulation of IL-6 expression might be used to prevent and treat HBV infection.
authors.affiliation: Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Guangzhou Medical University, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chest Surgery, Shenzhen People's Hospital, Jinan University, Shenzhen, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Clinical Laboratory, Guangzhou Medical University, Guangzhou, China.
authors.forename: A
authors.initials: A
authors.lastname: Wu
authors.affiliation: Department of Chest Surgery, Shenzhen People's Hospital, Jinan University, Shenzhen, China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: B
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D019562:Viral Load
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D015850:Interleukin-6; D000410:Alanine Transaminase