Search for new risk gene for chronic hepatitis B

• Project/Area Number: 25870178
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology; Medical genome science
• Research Institution: The University of Tokyo
• Principal Investigator: SAWAI Hiromi 東京大学, 医学(系)研究科(研究院), 特任助教 (60377124)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 肝臓学 / Ｂ型肝炎 / 疾患関連遺伝子 / 個別化医療 / B型肝炎 / HBV / 慢性化 / HLA

Outline of Final Research Achievements

We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and their haplotypes with hepatitis B virus infection and healthy control samples among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. Association analyses identified a new risk allele HLA-DPB1*09:01, and new protective alleles DPB1*02:01 and DPB1*04:01 to chronic HBV infection in addition to the previously reported alleles. Moreover, to identify new host genetic factors contributing to HBV infection, we conducted genome-wide association study (GWAS) and replication analyses using Japanese, Korean, Hong Kong, and Thai individuals. We unfortunately did not replicate the GWAS result although we could identify 529 SNPs with P < 10-4 in the GWAS stage.

Research Products

• [Journal Article] High-accuracy imputation for HLA class I and II genes based on high-resolution SNP data of population-specific references. (2015)
  • Author(s): Khor SS, Yang W, Kawashima M, Kamitsuji S, Zheng X, Nishida N, Sawai H, Toyoda H, Miyagawa T, Honda M, Kamatani N, Tokunaga K.
  • Journal Title: Pharmacogenomics J. Volume: 未定 Issue: 6 Pages: 1-8
  • DOI: 10.1038/tpj.2015.4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia. (2014)
  • Author(s): Nishida N, Sawai H, Kashiwase K, Minami M, Sugiyama M, Seto WK, Yuen MF, Posuwan N, Poovorawan Y, Ahn SH, Han KH, Matsuura K, Tanaka Y, Kurosaki M, Asahina Y, Izumi N, Kang JK, （省略）, Tokunaga K, and Mizokami M
  • Journal Title: PLoS One Volume: 9 Issue: 2 Pages: e86449-e86449
  • DOI: 10.1371/journal.pone.0086449
  • Peer Reviewed / Open Access
• [Presentation] Associations of HLA-DPB1 with CHB infection and HBV related HCC in Asia (2014)
  • Author(s): Nao Nishida, Hiromi Sawai, Koichi Kashiwase, Mutsuhiko Minami, Ken Yamamoto, et al.
  • Organizer: American Association for the study of Liver Diseases The Liver Meeting
  • Place of Presentation: Boston (USA)
  • Year and Date: 2014-11-07 – 2014-11-11
• [Presentation] Association of HLA-DPB1 alleles with CHB infection and HBV related HCC in Asia (2014)
  • Author(s): Nao Nishida, Hiromi Sawai, Kouich Kashiwase, Masaya Sugiyama, Yoriko Mawatari, Katsushi Tokunaga, Masashi Mizokami
  • Organizer: 62th Annual ASHG Meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-10-18 – 2014-10-22
• [Presentation] B型肝炎慢性化および病態進展に関わるHLA-DPアリルの横断的解析 (2014)
  • Author(s): 西田奈央、澤井裕美、杉山真也、馬渡頼子、徳永勝士、溝上雅史
  • Organizer: 第50回 日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ（東京、千代田区）
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] ゲノムワイド関連解析によるB型肝炎の慢性化および癌化に関わる新規遺伝要因の探索 (2014)
  • Author(s): 澤井裕美、西田奈央、田中靖人、溝上雅史、徳永勝士
  • Organizer: 第50回 日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ（東京、千代田区）
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] 中国集団におけるHBV陽性肝癌感受性候補SNPの東アジア集団での検証 (2013)
  • Author(s): 澤井裕美、西田奈央、松田浩一、馬渡頼子、田中靖人、溝上雅史、徳永勝士
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] Trans-ethnic analyses of HLA-DPA1, DPB1 haplotypes to be associated with hepatitis B virus infection (2013)
  • Author(s): Nao Nishida, Hiromi Sawai, Kouichi Kashiwase, Mutsuhiko Minami, Masaya Sugiyama, Wai-Kay Seto, Man-Fung Yuen, Yong Poovorawan, Sang Hoon Ahn, Kwang-Hyub Han, et al.
  • Organizer: American Association for the study of Liver Diseases The Liver Meeting 2013
  • Place of Presentation: Washington DC
• [Presentation] B型肝炎慢性化および病態進展に関わるHLA-DP遺伝子のアジア人集団における横断的解析 (2013)
  • Author(s): 西田奈央、澤井裕美、馬渡頼子、杉山真也、川嶋実苗、大橋順、田中靖人、徳永勝士、溝上雅史
  • Organizer: 日本人類遺伝学会 第58回大会
  • Place of Presentation: 仙台
• [Presentation] アジア人集団におけるB型肝炎患者を対象としたHLA-DP遺伝子の横断的解析 (2013)
  • Author(s): 西田奈央、澤井裕美、馬渡頼子、杉山真也、川嶋実苗、大橋順、田中靖人、徳永勝士、溝上雅史
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Remarks] 1-2．B型肝炎・C型肝炎に関連する遺伝要因の探索
  • URL: http://www.humgenet.m.u-tokyo.ac.jp/research/1-2.html
• [Patent(Industrial Property Rights)] B型肝炎の慢性化の素因の検出方法 (2013)
  • Inventor(s): 徳永勝士、澤井裕美、溝上雅史、西田奈央
  • Industrial Property Rights Holder: 徳永勝士、澤井裕美、溝上雅史、西田奈央
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-179634
  • Filing Date: 2013-08-30