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

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.

• Authors: Yoichiro Kamatani, Sukanya Wattanapokayakit, Hidenori Ochi, Takahisa Kawaguchi, Atsushi Takahashi, Naoya Hosono, Michiaki Kubo, Tatsuhiko Tsunoda, Naoyuki Kamatani, Hiromitsu Kumada, Aekkachai Puseenam, Thanyachai Sura, Yataro Daigo, Kazuaki Chayama, Wasun Chantratita, Yusuke Nakamura, Koichi Matsuda
• Journal: Nature genetics (Nat Genet) Vol. 41 Issue 5 Pg. 591-5 (May 2009) ISSN: 1546-1718 [Electronic] United States
• PMID: 19349983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Asian People (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