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

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

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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 individuals1. 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 × 10-39 and 2.31 × 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.

Original languageEnglish
Pages (from-to)591-595
Number of pages5
JournalNature Genetics
Volume41
Issue number5
DOIs
Publication statusPublished - 01-05-2009

All Science Journal Classification (ASJC) codes

  • Genetics

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    Kamatani, Y., Wattanapokayakit, S., Ochi, H., Kawaguchi, T., Takahashi, A., Hosono, N., Kubo, M., Tsunoda, T., Kamatani, N., Kumada, H., Puseenam, A., Sura, T., Daigo, Y., Chayama, K., Chantratita, W., Nakamura, Y., & Matsuda, K. (2009). A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nature Genetics, 41(5), 591-595. https://doi.org/10.1038/ng.348