A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians

Nat Genet. 2009 May;41(5):591-5. doi: 10.1038/ng.348. Epub 2009 Apr 6.

Abstract

Chronic hepatitis B is a serious infectious liver disease that often progresses to liver cirrhosis and hepatocellular carcinoma; however, clinical outcomes after viral exposure vary enormously among individuals. Through a two-stage genome-wide association study using 786 Japanese chronic hepatitis B cases and 2,201 controls, we identified a significant association of chronic hepatitis B with 11 SNPs in a region including HLA-DPA1 and HLA-DPB1. We validated these associations by genotyping two SNPs from the region in three additional Japanese and Thai cohorts consisting of 1,300 cases and 2,100 controls (combined P = 6.34 x 10(-39) and 2.31 x 10(-38), OR = 0.57 and 0.56, respectively). Subsequent analyses revealed risk haplotypes (HLA-DPA1(*)0202-DPB1(*)0501 and HLA-DPA1(*)0202-DPB1(*)0301, OR = 1.45 and 2.31, respectively) and protective haplotypes (HLA-DPA1(*)0103-DPB1(*)0402 and HLA-DPA1(*)0103-DPB1(*)0401, OR = 0.52 and 0.57, respectively). Our findings show that genetic variants in the HLA-DP locus are strongly associated with risk of persistent infection with hepatitis B virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group / genetics*
  • Cohort Studies
  • Genetics, Population
  • Genome, Human
  • Genome-Wide Association Study*
  • Genotype
  • HLA-DP Antigens / genetics*
  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • Haplotypes
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Linkage Disequilibrium
  • Polymorphism, Single Nucleotide*

Substances

  • HLA-DP Antigens
  • HLA-DP alpha-Chains
  • HLA-DP beta-Chains
  • HLA-DPA1 antigen
  • HLA-DPB1 antigen