A promoter polymorphism in the interferon alpha-2 gene is associated with the clinical presentation of hepatitis B.
Cytokine gene polymorphisms influence the severity of infectious diseases of viral and parasitic origin. Interferon alpha (IFN-alpha) is known to be involved in the defence against hepatitis B. The promoter of the IFN-alpha-2 gene was investigated for mutations in 344 hepatitis B virus (HBV)-infected Vietnamese patients and 293 uninfected Vietnamese. We found a deletion in the promoter, which was present significantly more frequently in HBV-infected patients than in control individuals; 20% of the healthy, whereas 35% of the HBV-infected cohort carries this deletion (P<0.001). Reporter gene assays showed that a construct with the deletion had a lower level of transcription in comparison to the wild type (P=0.011). These findings indicate that the deletion in the promoter of the IFN-alpha-2 gene reduces the transcription of this gene in vitro. This reduction could explain the individually different interferon levels in humans and could also be one cause of susceptibility to hepatitis B.
Song
Le H
le H
Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, Tübingen, Germany.
Toan
Nguyen L
NL
Xuan
Nguyen T
NT
Uhlemann
Anne-Catrin
AC
Boldt
Angelica B W
AB
Duy
Dinh N
DN
Binh
Vu Q
VQ
Kremsner
Peter G
PG
Kun
Jürgen F J
JF
D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006509:Hepatitis B / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods; D014744:Vietnam
D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D008156:Luciferases