title: A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers.
abstract: OBJECTIVE
  Chronic infection with the hepatitis B virus (HBV) is a major health issue worldwide. Recently, single nucleotide polymorphisms (SNPs) within the human leukocyte antigen (HLA)-DP locus were identified to be associated with HBV infection in Asian populations. Most significant associations were observed for the A alleles of HLA-DPA1 rs3077 and HLA-DPB1 rs9277535, which conferred a decreased risk for HBV infection. We assessed the implications of these variants for HBV infection in Caucasians.
  
  
  METHODS
  Two HLA-DP gene variants (rs3077 and rs9277535) were analyzed for associations with persistent HBV infection and with different clinical outcomes, i.e., inactive HBsAg carrier status versus progressive chronic HBV (CHB) infection in Caucasian patients (n = 201) and HBsAg negative controls (n = 235).
  
  
  RESULTS
  The HLA-DPA1 rs3077 C allele was significantly associated with HBV infection (odds ratio, OR = 5.1, 95% confidence interval, CI: 1.9-13.7; p = 0.00093). However, no significant association was seen for rs3077 with progressive CHB infection versus inactive HBsAg carrier status (OR = 2.7, 95% CI: 0.6-11.1; p = 0.31). In contrast, HLA-DPB1 rs9277535 was not associated with HBV infection in Caucasians (OR = 0.8, 95% CI: 0.4-1.9; p = 1).
  
  
  CONCLUSIONS
  A highly significant association of HLA-DPA1 rs3077 with HBV infection was observed in Caucasians. However, as a differentiation between different clinical courses of HBV infection was not possible, knowledge of the HLA-DPA1 genotype cannot be translated into personalized anti-HBV therapy approaches.
authors.affiliation: pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der J. W. Goethe Universität, Frankfurt am Main, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vermehren
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
authors.forename: Simone
authors.initials: S
authors.lastname: Susser
authors.forename: Sabine
authors.initials: S
authors.lastname: Wicker
authors.forename: Annemarie
authors.initials: A
authors.lastname: Berger
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Doehring
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059867:HLA-DP alpha-Chains / Q000235:genetics*; D006239:Haplotypes; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D004279:DNA, Viral; D059867:HLA-DP alpha-Chains; C071172:HLA-DPA1 antigen; D006514:Hepatitis B Surface Antigens