title: Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection.
abstract: OBJECTIVE
  Exposure to HBV leads to a distinct clinical course which is partially pertained to host genetic variability. We aimed to study polymorphisms of type I interferon receptor 1 (IFNAR1) promoter and their potential effects on chronic HBV infection.
  
  
  METHODS
  Polymorphisms of IFNAR1 promoter were identified in 320 chronic hepatitis B patients, 148 spontaneously recovered individuals, 148 healthy Chinese donors and 114 Caucasians. Their functional capability in driving reporter gene expression was analyzed.
  
  
  RESULTS
  Four polymorphic alleles were identified at loci -568, -408, -77 and -3. Association analysis revealed that carriers of alleles -568G, -408C and their related haplotype I were less susceptible to chronic HBV infection whereas those of alleles -568C, -408T and related haplotype III were significantly associated with higher risk to chronic hepatitis B (P<0.01). In a reporter-driven system, the promoter variants with alleles -408C and -3C could drive higher expression of the reporter gene than those with alleles -408T and -3T (P<0.01). Interestingly, an allele with 9 GT repeats at -77 that was rarely found in Chinese but prevalent in Caucasian exhibited the highest transcriptional ability.
  
  
  CONCLUSIONS
  Our results showed that polymorphisms of IFNAR1 promoter may affect, at least in part, the outcomes of HBV infection.
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
authors.forename: Ting-Wa
authors.initials: TW
authors.lastname: Lam
authors.forename: Chi-Ping
authors.initials: CP
authors.lastname: Chung
authors.forename: Chun-Lit
authors.initials: CL
authors.lastname: Lam
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Sharon H W
authors.initials: SH
authors.lastname: Wu
authors.forename: Vincent K M
authors.initials: VK
authors.lastname: Poon
authors.forename: Fai
authors.initials: F
authors.lastname: Ng
authors.forename: Chris C S
authors.initials: CC
authors.lastname: Chan
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
authors.forename: Bo-Jian
authors.initials: BJ
authors.lastname: Zheng
mesh_terms: D044466:Asian People / Q000235:genetics; D003289:Convalescence; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C507964:IFNAR1 protein, human; D053633:Receptor, Interferon alpha-beta