Host genetic factors associated with drug response and side effects against HCV treatment

• Project/Area Number: 24790728
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: 独立行政法人国立国際医療研究センター
• Principal Investigator: NISHIDA NAO 独立行政法人国立国際医療研究センター, その他部局等, 上級研究員 (50456109)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肝臓学 / 疾患関連遺伝子 / GWAS / 肝炎 / HCV / 薬剤応答性 / 副作用

Research Abstract

We identified the host genetic factors associated with side effects (anemia, neutropenia) against HCV treatment. These findings would enable to make selection of patients who will get successful treatment or who have few side-effects, by testing newly identified host genetic markers in combination with IL28B SNP. Moreover, we identified the association of HLA-DQB1 allele with HCV spontaneous clearance in Japanese HCV patients. DQB1 alleles would be key host factors to clear HCV, which will lead the following functional studies of HLA-DQ molecules in the future.

Research Products

• [Journal Article] The interaction of a single-nucleotide polymorphism with age on response to interferon-α and ribavirin therapy in female patients with hepatitis C infection. (2014)
  • Author(s): Nishino J, Sugiyama M, Nishida N, Tokunaga K, Mizokami M, Mano S
  • Journal Title: J Med Virol Volume: 86(7) Issue: 7 Pages: 1130-3
  • DOI: 10.1002/jmv.23939
  • Peer Reviewed
• [Journal Article] IL28B polymorphisms and clinical implications for hepatitis C virus infection in Uzbekistan (2014)
  • Author(s): Khudayberganova D, Sugiyama M, Masaki N, Nishida N, Mukaide M, Sekler D, Latipov R, Nataliya K, Dildora S, Sharapov S, Usmanova G, Raxmanov M, Musabaev E, Mizokami M
  • Journal Title: PLoS One Volume: 24;9 Issue: 3 Pages: e93011-e93011
  • DOI: 10.1371/journal.pone.0093011
  • Peer Reviewed / Open Access
• [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
• [Journal Article] Genome-Wide Association Study Reveals Host Genetic Factors for Liver Diseases (2013)
  • Author(s): Nishida N, Tokunaga K, et al. (他1名)
  • Journal Title: Journal of Clinical and Translational Hepatology Volume: 1 Pages: 45-50
  • Peer Reviewed
• [Journal Article] Model incorporating the ITPA genotype identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C. (2013)
  • Author(s): Kurosaki M, Sakamoto N, Asahina Y, Izumi N et al
  • Journal Title: J Med Virol Volume: 85 Issue: 3 Pages: 449-458
  • DOI: 10.1002/jmv.23497
  • Peer Reviewed
• [Journal Article] The history of human populations in the Japanese Archipelago inferred from genome-wide SNP data with a special reference to the Ainu and the Ryukyuan Populations. (2012)
  • Author(s): Jinam T, Nishida N, Hirai M, Kawamura S, Oota H, Umetsu K, Kimura R, Ohashi J, Tajima A, Yamamoto T, Tanabe H, Mano S, Suto Y, Kaname T, Naritomi K, Yanagi K, Niikawa N, Omoto K. Saitou N
  • Journal Title: Journal of Human Genetics Volume: 57巻 Issue: 12 Pages: 787-79
  • DOI: 10.1038/jhg.2012.114
  • NAID: 10031145887
  • Peer Reviewed
• [Journal Article] Evolutionary analysis of classical HLA class I and II genes suggests that recent positive selection acted on DPB1*04 : 01 in Japanese population (2012)
  • Author(s): Kawashima M, Nishida N, et al. (他2名)
  • Journal Title: PLoS One Volume: 7(10) Issue: 10 Pages: e46806-e46806
  • DOI: 10.1371/journal.pone.0046806
  • NAID: 120007137181
  • Peer Reviewed
• [Journal Article] Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population. (2012)
  • Author(s): Nakamura M
  • Journal Title: Am J Hum Genet. Volume: 91 Issue: 4 Pages: 721-728
  • DOI: 10.1016/j.ajhg.2012.08.010
  • Peer Reviewed
• [Journal Article] Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. (2012)
  • Author(s): Nishida N, Asahina Y, Mizokami M et al
  • Journal Title: PLoS One Volume: 7 Issue: 6 Pages: 1-8
  • DOI: 10.1371/journal.pone.0039175
  • Peer Reviewed
• [Journal Article] No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations. (2012)
  • Author(s): Sawai H, Asahina Y, Tokunaga K et al
  • Journal Title: BMC Med Genet Volume: 13 Issue: 1 Pages: 47-47
  • DOI: 10.1186/1471-2350-13-47
  • Peer Reviewed
• [Journal Article] Highly parallel and short-acting amplification with locus-specific primers to detect single nucleotide polymorphisms by the DigiTag2 assay (2012)
  • Author(s): Nishida et al.
  • Journal Title: PLoS One Volume: 7 Issue: 1 Pages: e29967-e29967
  • DOI: 10.1371/journal.pone.0029967
  • Peer Reviewed
• [Presentation] HLA アリルでの層別解析に よるB 型肝炎慢性化およびウイルス排 除に関わる宿主遺伝子の探索 (2014)
  • Author(s): 西田奈央
  • Organizer: 「Liver Forum in Kyoto」第16回学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-03-29
  • Invited
• [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] IL28B 遺伝子によるC 型肝炎の治療効果予測と第二の関連遺伝子の探索 (2013)
  • Author(s): 西田奈央, 徳永勝士, 溝上雅史, , ,
  • Organizer: 第17回日本肝臓学会大会
  • Place of Presentation: 品川
• [Presentation] Development of DigiTag2 for determination of human SNPs , The Symposium on SNP typing : Application in human and TB (2013)
  • Author(s): Nao Nishida
  • Organizer: International Conference in Medicine and Public Health 2013
  • Place of Presentation: Bangkok
  • Invited
• [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
  • Place of Presentation: 神戸
• [Presentation] Understanding of IL28B gene associated with treatment response for HCV patients (2013)
  • Author(s): Nao Nishida, Yasuhito Tanaka, Masaya Sugiyama, Yoriko Mawatari, Mayumi Ishii, Chieko Haga, Katsushi Tokunaga, Masashi Mizokami
  • Organizer: 61th Annual ASHG Meeting
  • Place of Presentation: Boston
• [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, Kentaro Matsuura, Yasuhito Tanaka, Masayuki Kurosaki, Yasuhiro Asahina, Namiki Izumi, Jong-Hon Kang, Shuhei Hige, Tatsuya Ide, Kazuhide Yamamoto, Isao Sakaida, Yoshikazu Murawaki, Yoshito Itoh, Akihiro Tamori, Etsuro Orito, Yoichi Hiasa, Masao Honda, Shuichi Kaneko, Eiji Mita, Kazuyuki Suzuki, Keisuke Hino, Eiji Tanaka, Satoshi Mochida, Masaaki Watanabe, Yuichiro Eguchi, Masaaki Korenaga, Yoriko Mawatari, Minae Kawashima, Katsushi Tokunaga, Masashi Mizokami
  • Organizer: American Association for the study of Liver Diseases The Liver Meeting 2013
  • Place of Presentation: Washington DC
• [Presentation] C 型慢性肝炎の治療効果に関連する第二遺伝要因の探索 (2013)
  • Author(s): 西田奈央,田中靖人, 杉山真也, 馬渡頼子, 石井真由美, 徳永勝士, 溝上雅史
  • Organizer: 第49回日本肝臓学会総会
  • Place of Presentation: 新宿
• [Presentation] IL28B遺伝子によるC型肝炎の治療効果予測と、第二の関連遺伝子の探索 (2013)
  • Author(s): 西田奈央、徳永勝士、溝上雅史
  • Organizer: 第17回日本肝臓学会大会
  • Place of Presentation: 品川
  • Invited
• [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] ウイルス性肝炎にみる宿主因子とウイルス因子 (2012)
  • Author(s): 西田奈央
  • Organizer: 日本人 類遺伝学会 第57回大会 シンポジウム7 感染症の遺伝学:ゲノムと環境の相互作用
  • Place of Presentation: 新宿
  • Invited
• [Presentation] Genome-wide association study (GWAS) による日本人原発性肝硬変 (PBC)の疾患感受性遺伝子の同定 (2012)
  • Author(s): 西田奈央, 川嶋実苗, 馬渡頼子, 相葉佳洋, 小森敦正, 徳永勝士, 中村 稔
  • Organizer: 第35回日本分子生物学会年
  • Place of Presentation: 福岡
• [Presentation] DigiTag2法における PCR プライマー設計パラメータの検証 (2012)
  • Author(s): 馬渡頼子, 西田奈央, 中伊津美, 徳永勝士, 溝上雅史
  • Organizer: 第35回日本分子生物学会年
  • Place of Presentation: 福岡
• [Presentation] 東 アジア集団におけるB型肝炎慢性化、 HBV排除を規定するHLA-DP遺伝子の同定 (2012)
  • Author(s): 西田奈央, 田中靖人, 澤井裕美, 杉山真 也, 馬渡頼子, 徳永勝士, 溝上雅史
  • Organizer: 第35回日本分子生物学会年
  • Place of Presentation: 福岡
• [Presentation] Investigating the novel host genetic factors associated with treatment response for HCV patients (2012)
  • Author(s): Nao Nishida, Yasuhito Tanaka, Masaya Sugiyama, Yoriko Mawatari, Mayumi Ishii, Katsushi Tokunaga, Masashi Mizokami
  • Organizer: The 10th JSH Single Topic Conference "Hepatitis C: Best Practice Based on Science"
  • Place of Presentation: 新宿
• [Presentation] Meta-analysis identifies the association of HLA-DP locus with chronic hepatitis B and viral clearance widely in East-Asian populations (2012)
  • Author(s): Nao Nishida, Yasuhito Tanaka, Hiromi Sawai, Yoriko Mawatari, Megumi Yamaoka, Kentaro Matsuura, Masaya Sugiyama, Kazumoto Murata, Masaaki Korenaga, Naohiko Masaski, Kwang-Hyub Han, Katsushi Tokunaga, Masashi Mizokami
  • Organizer: American Association for the study of Liver Diseases The Liver Meeting 2012
  • Place of Presentation: Boston
• [Presentation] The associations of HLA-DP locus with chronic hepatitis B and viral clearance are widely replicated in East-Asian populations (2012)
  • Author(s): Nao Nishida, Yasuhito Tanaka, Hiromi Sawai, Yoriko Mawatari, Megumi Yamaoka, Asako Koike, Kentaro Matsuura, Masaya Sugiyama, Kazumoto Murata, Masaaki Korenaga, Naohiko Masaski, Kwang-Hyub Han, Katsushi Tokunaga, Masashi Mizokami
  • Organizer: 61th Annual ASHG Meeting
  • Place of Presentation: San Fransisco
• [Presentation] 日本人および韓国人におけるB 型肝炎慢性化、B型肝炎ウイルス排除を規定するHLA-DP遺伝子の同定 (2012)
  • Author(s): 西田奈央, 田中靖人, 澤井裕美, 杉山真也, 馬渡頼子, 徳永勝士, 溝上雅史
  • Organizer: 第16回日本肝臓学会大会(JDDW)
  • Place of Presentation: 神戸
• [Presentation] ウイルス性肝炎にみる宿主因子とウイルス因子 (2012)
  • Author(s): 西田奈央
  • Organizer: 日本人類遺伝学会 第57回大会
  • Place of Presentation: 京王プラザホテル（新宿）
  • Invited
• [Presentation] 日本人および韓国人におけるB型肝炎慢性化、B型肝炎ウイルス排除を規定するHLA-DP遺伝子の同定 (2012)
  • Author(s): 西田奈央、田中靖人、澤井裕美、杉山真也、馬渡頼子、徳永勝士、溝上雅史
  • Organizer: 第16回日本肝臓学会大会（JDDW）
  • Place of Presentation: 神戸国際展示場、ポートピアホテル、神戸国際会議場
• [Presentation] Meta-analysis identifies the association of HLA-DP locus with chronic hepatitis B and viral clearance widely in East-Asian populations (2012)
  • Author(s): Nao Nishida, Yasuhito Tanaka, Hiromi Sawai, et al.
  • Organizer: American Association for the study of Liver Diseases The Liver Meeting 2012
  • Place of Presentation: Boston, Hynes Convention Center
• [Presentation] Investigating the novel host genetic factors associated with treatment response for HCV patients (2012)
  • Author(s): Nao Nishida, Yasuhito Tanaka, Masaya Sugiyama, Yoriko Mawatari, Mayumi Ishii, Katsushi Tokunaga, Masashi Mizokami
  • Organizer: The 10th JSH Single Topic Conference "Hepatitis C: Best Practice Based on Science"
  • Place of Presentation: 京王プラザホテル(新宿)
• [Presentation] 東アジア集団におけるB型肝炎慢性化、HBV排除を規定するHLA-DP遺伝子の同定（英文表題: Association of HLA-DP variants with chronic hepatitis B and viral clearance in East Asian populations） (2012)
  • Author(s): 西田奈央、田中靖人、澤井裕美、杉山真也、馬渡頼子、徳永勝士、溝上雅史
  • Organizer: 第35回日本分子生物学会年
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
• [Presentation] DigiTag2法におけるPCRプライマー設計パラメータの検証 (2012)
  • Author(s): 馬渡頼子、西田奈央、中伊津美、徳永勝士、溝上雅史
  • Organizer: 第35回日本分子生物学会年
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
• [Presentation] Genome-wide association study (GWAS)による日本人原発性肝硬変（PBC）の疾患感受性遺伝子の同定 (2012)
  • Author(s): 西田奈央、川嶋実苗、馬渡頼子、相葉佳洋、小森敦正、徳永勝士、中村 稔
  • Organizer: 第35回日本分子生物学会年
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡
• [Presentation] HLAアリルでの層別解析によるB型肝炎慢性化およびウイルス排除に関わる宿主遺伝子の探索
  • Author(s): 西田奈央
  • Organizer: 「Liver Forum in Kyoto」第16回学術集会
  • Place of Presentation: 京都
  • Invited
• [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