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Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean

Authors
 Nao Nishida ; Hiromi Sawai ; Masashi Mizokami ; Katsushi Tokunaga ; Yasuhito Tanaka ; Kwang-Hyub Han ; Namiki Izumi ; Asako Koike ; Yuko Ogasawara ; Megumi Sageshima ; Yoriko Mawatari ; Minae Kawashima ; Tatsuya Ide ; Keisuke Hino ; Masaaki Korenaga ; Isao Sakaida ; Yoichi Hiasa ; Yoshikazu Murawaki ; Akihiro Tamori ; Eiji Mita ; Yoshito Itoh ; Etsuro Orito ; Shuichi Kaneko ; Masao Honda ; Eiji Tanaka ; Masaaki Watanabe ; Satoshi Mochida ; Yasuhiro Asahina ; Masayuki Kurosaki ; Kazuyuki Suzuki ; Jong-Hon Kang ; Shuhei Hige ; Jun Yong Park ; Sang Hoon Ahn ; Masaya Sugiyama ; Kentaro Matsuura 
Citation
 PLoS One, Vol.7(6) : e39175, 2012 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2012
Abstract
Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85-90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P(meta) = 1.89×10⁻¹² for rs3077 and P(meta) = 9.69×10⁻¹⁰ for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (P(meta) = 4.40×10⁻¹⁹ for rs3077 and P(meta) = 1.28×10⁻¹⁵ for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/91717
DOI
10.1371/journal.pone.0039175
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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