title: HLA-DP and IL28B polymorphisms: influence of host genome on hepatitis B surface antigen seroclearance in chronic hepatitis B.
abstract: BACKGROUND
  The roles of single-nucleotide polymorphisms (SNPs) at HLA-DP and IL28B loci on hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) infection are unknown.
  
  
  METHODS
  We compared the HLA-DP (rs3077, rs9277378, rs3128917) and IL28B (rs12979860, rs8099917) polymorphisms of 203 CHB patients achieving spontaneous HBsAg seroclearance with 203 age- and sex-matched CHB patients without HBsAg seroclearance (controls).
  
  
  RESULTS
  The distribution of all 5 polymorphisms was in Hardy-Weinberg equilibrium. HLA-DP rs3077 was associated with HBsAg seroclearance in terms of allelic frequency (minor allele A vs major allele G, P = .035; odds ratio [OR], 0.699; 95% confidence interval [CI], .501-.976) and genotypic frequency (AA vs GG/GA, P = .014; OR, 0.295; 95% CI, .106-.822). Haplotype analysis of HLA-DP polymorphisms showed haplotype block GAT (rs3077/rs9277378/rs3128917) to be associated with HBsAg seroclearance (OR, 2.17; 95% CI, 1.06-4.45, P = .034). Influence of HLA-DP polymorphisms on HBsAg seroclearance was more pronounced in younger patients, with the OR for rs3077 minor allele A and haplotype block GAT being 0.560 and 2.68, respectively, among patients aged <50 years (P = .027 and P = .047, respectively). IL28B haplotype block CG (rs12979860/rs8099917) was associated with HBsAg seroclearance (OR, 10.5, P = .026). None of the 5 polymorphisms influenced anti-HBs positivity among patients achieving HBsAg seroclearance, or serum HBV DNA and HBsAg titers among controls (P > .05).
  
  
  CONCLUSIONS
  Specific SNPs in HLA-DP and IL28B locus, through individual and haplotype analysis, were associated with a higher chance of HBsAg seroclearance in CHB infection. The associations were more prominent in patients with HBsAg seroclearance at a younger age.
authors: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors: Wai-Kay
authors: WK
authors: Seto
authors: Danny Ka-Ho
authors: DK
authors: Wong
authors: Malgorzata
authors: M
authors: Kopaniszen
authors: Petroula
authors: P
authors: Proitsi
authors: Pak-Chung
authors: PC
authors: Sham
authors: Ivan Fan-Ngai
authors: IF
authors: Hung
authors: James
authors: J
authors: Fung
authors: Ching-Lung
authors: CL
authors: Lai
authors: Man-Fung
authors: MF
authors: Yuen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood; D004843:Epistasis, Genetic; D005260:Female; D056726:Genetic Association Studies; D015894:Genome, Human; D006682:HLA-DP Antigens / Q000235:genetics*; D006239:Haplotypes; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000235:genetics* / Q000276:immunology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D004279:DNA, Viral; D006682:HLA-DP Antigens; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: HBV; HBsAg seroclearance; HLA; IL28B; SNP