title: Influence of a single nucleotide polymorphism in the P1 promoter of the furin gene on transcription activity and hepatitis B virus infection.
abstract: Hepatitis B e antigen (HBeAg) is a viral strategy of immune response evasion associated with hepatitis B virus (HBV) persistence. Spontaneous HBeAg seroconversion is usually accompanied by liver disease remission. Unfortunately, this goal is difficult to achieve and requires expensive and time-consuming treatment. Furin, a proprotein convertase, is involved in HBeAg maturation and is therefore a potential therapeutic target or indicator for predicting disease progression and antiviral response. Here we demonstrate that healthy Han Chinese from southern China (an endemic area of HBV infection) harbor a common single nucleotide polymorphism (SNP; -229 C/T) in a 1268-bp region of the P1 promoter of the furin gene [FES upstream region (Fur)]. A luciferase reporter gene assay showed that transcription activity is about 3 times higher in allele T carriers than in allele C carriers of this SNP. Allele T includes a suboptimal transcription factor NF-E2 [i.e., nuclear factor (erythroid-derived 2)]-binding motif according to bioinformatics and studies using site-directed mutagenesis. We also observed that individuals carrying allele T were more likely to become persistently infected. When persistently infected patients were divided into subgroups according to recent guidelines and HBeAg-defective virus infection was taken into account, patients with allele T or genotype TT had a decreased likelihood of HBeAg seroconversion or an increased likelihood of progressing to HBeAg-negative chronic hepatitis B or liver cirrhosis if accompanied by HBeAg-defective virus infection.
  
  
  CONCLUSIONS
  The common SNP in the P1 promoter of the Fur gene affects furin transcription activity and HBV infection outcome, possibly by increasing furin messenger RNA expression, and this suggests that furin is a potential therapeutic target and that this SNP is a potential predictor of disease progression or therapeutic response.
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital, Sun Yat-Sen University, People's Republic of China.
authors.forename: Rui Xiang
authors.initials: RX
authors.lastname: Lei
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Xiao Mou
authors.initials: XM
authors.lastname: Peng
authors.forename: Yin Hong
authors.initials: YH
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Gui Hua
authors.initials: GH
authors.lastname: Chen
mesh_terms: D000328:Adult; D005260:Female; D045683:Furin / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D006513:Hepatitis B e Antigens; D045683:Furin