Polymorphisms of type I interferon receptor 1 promoter and their effects on chronic hepatitis B virus infection

J Hepatol. 2007 Feb;46(2):198-205. doi: 10.1016/j.jhep.2006.08.017. Epub 2006 Oct 17.

Abstract

Background/aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Convalescence*
  • Female
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Linkage Disequilibrium
  • Male
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic / genetics
  • Receptor, Interferon alpha-beta / genetics*
  • Transcription, Genetic

Substances

  • IFNAR1 protein, human
  • Receptor, Interferon alpha-beta