title: Differential genetic determination of immune responsiveness to hepatitis B surface antigen and to hepatitis A virus: a vaccination study in twins.
abstract: BACKGROUND
  The course of viral hepatitis is thought to be affected by genetic host variability and, in particular, by genes of the major histocompatibility locus. Hepatitis A and B vaccination is a useful model to study the effect of host factors on the immune response to viral antigens. We aimed to assess the heritability of the HBsAg (anti-HBs) and anti-hepatitis A virus (anti-HAV) immune response and to estimate the effect of the HLA-DRB1 locus and other genetic loci unlinked to HLA.
  
  
  METHODS
  We did an open prospective study and vaccinated 202 twin pairs with a combined recombinant HBsAg/inactivated hepatitis A vaccine. We measured antibodies to HBsAg and HAV and determined HLA-DRB1* alleles. Heritability was calculated based on variance of antibody response within pairs. Model-fitting analyses were done to analyse genetic and environmental components of vaccine responses.
  
  
  RESULTS
  Anti-HBs and anti-HAV showed heritabilities of 0.61 (95% CI 0.41 to 0.81) and 0.36 (-0.02 to 0.73), respectively. For the anti-HBs immune response, 60% of the phenotypic variance was explained by additive genetic and 40% by non-shared environmental effects. The heritability of the HBsAg vaccine response accounted for by the DRB1* locus was estimated to be 0.25, leaving the remaining heritability of 0.36 to other gene loci.
  
  
  CONCLUSIONS
  Genetic factors have a strong effect on the immune response to HBsAg. Although genes encoded within the MHC are important for this immune response, more than half the heritability is determined outside this complex. Identification of these genes will help us to understand regulation of immune responses to viral proteins.
authors.affiliation: Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany. hoehler@mail.uni-mainz.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Höhler
authors.forename: Esther
authors.initials: E
authors.lastname: Reuss
authors.forename: Nina
authors.initials: N
authors.lastname: Evers
authors.forename: Evi
authors.initials: E
authors.lastname: Dietrich
authors.forename: Christian
authors.initials: C
authors.lastname: Rittner
authors.forename: Christine M
authors.initials: CM
authors.lastname: Freitag
authors.forename: Jens
authors.initials: J
authors.lastname: Vollmar
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schneider
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D035922:Hepatitis A Antibodies / Q000235:genetics; D030041:Hepatitis A virus / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000097:blood / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007110:Immunity, Active / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D018433:Twin Studies as Topic; D014611:Vaccination
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D035922:Hepatitis A Antibodies; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011994:Recombinant Proteins