title: Genetic variants in ERBB4 is associated with chronic hepatitis B virus infection.
abstract: BACKGROUND
  The role of ERBB4 in liver disease has seldom been reported. This study aims to find genetic markers at ERBB4 for chronic hepatitis B virus (HBV) infection and determine the role of ERBB4 in liver injury.
  
  
  METHODS
  We selected and genotyped three single nucleotide polymorphisms and one insertion/deletion (Ins/Del) at the 5' and 3' untranslated region (UTR) of ERBB4 in a case-control study including 1344 pairs of HBV carriers and HBV natural clearance subjects. The luciferase reporter system was applied to study the regulative role of Ins/Del on ERBB4. Further, ERBB4 knockout mice were used to study the role of ERBB4 in liver injury. Proteomic quantification was performed by HPLC-MS/MS analysis to identify liver protein profile change between liver-specific ERBB4 knockout and control mice.
  
  
  RESULTS
  rs6147150 Ins/Del and rs1836724 T>C at the 3' UTR of ERBB4 were associated with reduced risk of chronic HBV infection (P = 0.002 and 0.004, respectively). Besides, the 12bp deletion at the 3' UTR increased ERBB4 expression due to lacking let-7c binding site. In addition, loss of ERBB4 led to more severe acute or chronic inflammation in mouse liver injury models. Further, quantitative proteomic analysis and data from the cancer genome atlas revealed that ACLY, an enzyme key for de novo lipogenesis, was negatively correlated with ERBB4.
  
  
  CONCLUSIONS
  ERBB4 plays protective role from liver injury and its 3'UTR genetic variants could be genetic markers for chronic HBV infection.
authors.affiliation: Department of Pathology, Medical College of Soochow University, Suzhou 215123, People's Republic of China.|Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Medical College of Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Medical College of Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Xiao-Shun
authors.initials: XS
authors.lastname: He
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Song
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology, Medical College of Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Wei-Juan
authors.initials: WJ
authors.lastname: Jiao
authors.affiliation: Department of Pathology, Medical College of Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Tong
authors.initials: T
authors.lastname: Shen
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
authors.forename: Su
authors.initials: S
authors.lastname: Yao
authors.affiliation: Department of Pathology, Medical College of Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, People's Republic of China.
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Hu
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Gao
authors.affiliation: Department of Pathology, Medical College of Soochow University, Suzhou 215123, People's Republic of China.|Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Li
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006367:HeLa Cells; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000821:virology*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D008107:Liver Diseases / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D066247:Receptor, ErbB-4 / Q000235:genetics* / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: C587689:ERBB4 protein, human; D066247:Receptor, ErbB-4
keywords: ERBB4; hepatitis B virus; inflammation; polymorphism