次世代大規模シークエンジング技術による慢性ウイルス性肝疾患の病態解明

2011 年度 研究成果報告書

• 研究課題/領域番号: 21659186
• 研究種目: 挑戦的萌芽研究
• 配分区分: 補助金
• 研究分野: 消化器内科学
• 研究機関: 山梨大学
• 研究代表者: 榎本 信幸 山梨大学, 大学院・医学工学総合研究部, 教授 (20251530)
• 研究分担者: 前川 伸哉 山梨大学, 大学院・医学工学総合研究部, 講師 (70397298)
• 研究期間 (年度): 2009 – 2011
• キーワード: HCV / HBV / 次世代シークエンス / deep sequencing

研究概要

次世代高速シークエンサーであるRoche Genome Sequencer Junior(GSJ)を用いて患者体内の肝炎ウイルス遺伝子の大規模高速塩基配列解析方法を開発、C型肝炎ウイルス(HCV)のコア遺伝子、NS3遺伝子、NS5A遺伝子、およびB型肝炎ウイルス(HBV)のpreS遺伝子のdeep sequencingによる解析を行い、治療、耐性化、病変進展、発癌などに伴い変異体の構成が動的に変化することを明らかとした。

研究成果

• [雑誌論文] Correlation between Pretreatment Viral Sequences and the Emergence of Lamivudine Resistance in Hepatitis B Virus Infection. (2012)
  • 著者名/発表者名: Sueki R, Maekawa S, Miura M, Kadokura M, Komase K, Shindo H, Kanayama A, Ohmori T, Shindo K, Amemiya F, Nakayama Y, Uetake T, Inoue T, Sakamoto M, Enomoto N.
  • 雑誌名: J Med Virol 巻: (in press)
  • 査読あり
• [雑誌論文] Association of geneexpression involving innate immunity and genetic variation in interleukin 28Bwith antiviral response. (2012)
  • 著者名/発表者名: Asahina Y, Tsuchiya K, Muraoka M, Tanaka K, Suzuki Y, Tamaki N, Hoshioka Y, Yasui Y, KatohT, Hosokawa T, Ueda K, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Nitta S, Sakamoto N, Izumi N.
  • 雑誌名: Hepatology 巻: 55(1) ページ: 20-9
  • DOI: DOI:10.1002/hep.24623.
  • 査読あり
• [雑誌論文] Pre-treatment prediction of response to pegylated-interferon plus ribavirin forchronic hepatitis C using genetic polymorphism in IL28B and viral factors. (2011)
  • 著者名/発表者名: Kurosaki M, Tanaka Y, Nishida N, SakamotoN, Enomoto N, Honda M, Sugiyama M, Matsuura K, Sugauchi F, Asahina Y, NakagawaM, Watanabe M, Sakamoto M, Maekawa S, SakaiA, Kaneko S, Ito K, Masaki N, Tokunaga K, Izumi N, Mizokami M.
  • 雑誌名: J Hepatol 巻: 54(3) ページ: 439-48
  • 査読あり
• [雑誌論文] Analysis of the complete open reading frame of hepatitis C virus in genotype 2ainfection reveals critical sites influencing the response to peginterferon andribavirin therapy. (2011)
  • 著者名/発表者名: Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, SakamotoN, Watanabe M, Enomoto N.
  • 雑誌名: Hepatol Int 巻: 5(3) ページ: 789-99
  • 査読あり
• [雑誌論文] Relationship between polymorphisms of theinosine triphosphatase geneand anaemia or outcome after treatment with pegylated interferon and ribavirin. (2011)
  • 著者名/発表者名: Kurosaki M, Tanaka Y, Tanaka K, Suzuki Y, Hoshioka Y, Tamaki N, Kato T, Yasui Y, Hosokawa T, Ueda K, Tsuchiya K, Kuzuya T, Nakanishi H, Itakura J, Takahashi Y, Asahina Y, Matsuura K, Sugauchi F, Enomoto N, Nishida N, Tokunaga K, Mizokami M, Izumi N.
  • 雑誌名: Antivir Ther 巻: 16(5) ページ: 685-94
  • 査読あり
• [雑誌論文] Analysis of the complete open reading frame of genotype 2b hepatitis C virus inassociation with the response to peginterferon and ribavirin therapy. (2011)
  • 著者名/発表者名: Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, UetakeT, Inoue T, Sakamoto M, Nakagawa M, SakamotoN, Watanabe M, Enomoto N.
  • 雑誌名: PLoS One 巻: 6(9) ページ: e24514
  • 査読あり
• [雑誌論文] Characterization of naturally occurring proteaseinhibitor-resistance mutations in genotype 1b hepatitis C virus patients. (2011)
  • 著者名/発表者名: Shindo H, Maekawa S, Komase K, Sueki R, Miura M, Kadokura M, Shindo K, Amemiya F, Kitamura T, Nakayama Y, Inoue T, Sakamoto M, Okada SI, Asahina Y, Izumi N, Honda M, Kaneko S, Enomoto N.
  • 雑誌名: Hepatol Int
  • 査読あり
• [雑誌論文] Analysis of viral amino acids sequences and the IL28B SNP in fluencing the development of hepatocellular carcinoma in chronic hepatitis C. (2011)
  • 著者名/発表者名: Miura M, Maekawa S, Kadokura M, Sueki R, Komase K, Shindo H, Ohmori T, Kanayama A, Shindo K, Amemiya F, Nakayama Y, Kitamura T, Uetake T, Inoue T, Sakamoto M, Okada S, Enomoto N
  • 雑誌名: Hepatol Int
  • 査読あり
• [雑誌論文] HCV genetic elements determining the early response to peginterferon and ribavirin therapy. (2010)
  • 著者名/発表者名: Enomoto N, Maekawa S.
  • 雑誌名: Intervirology 巻: 53(1) ページ: 66-9
  • 査読あり
• [雑誌論文] A predictive model of response to peginterferon ribavirin in chronic hepatitis C using classification andregression tree analysis. (2010)
  • 著者名/発表者名: Kurosaki M, Matsunaga K, Hirayama I, Tanaka T, Sato M, Yasui Y, Tamaki N, Hosokawa T, Ueda K, Tsuchiya K, Nakanishi H, Ikeda H, Itakura J, Takahashi Y, Asahina Y, Higaki M, Enomoto N, Izumi N.
  • 雑誌名: Hepatol Res 巻: 40(3) ページ: 251-60
  • 査読あり
• [雑誌論文] Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection. (2010)
  • 著者名/発表者名: Nakagawa M, Sakamoto N, Ueyama M, Mogushi K, Nagaie S, Itsui Y, Azuma S, Kakinuma S, Tanaka H, Enomoto N, WatanabeM.
  • 雑誌名: J Gastroenterol 巻: 45(6) ページ: 656-65
  • 査読あり
• [雑誌論文] ITPA gene variant protects against anemia induced by pegylated interferon-αand ribavirin therapy for Japanese patients with chronic hepatitis C. (2010)
  • 著者名/発表者名: Sakamoto N, Tanaka Y, Nakagawa M, Yatsuhashi H, Nishiguchi S, Enomoto N, AzumaS, Nishimura-Sakurai Y, Kakinuma S, Nishida N, Tokunaga K, Honda M, Ito K, Mizokami M, Watanabe M.
  • 雑誌名: Hepatol Res 巻: 40(11) ページ: 1063-1071
  • 査読あり
• [学会発表] Analysis of theearly response and the final outcome topegylated-interferon plus ribavirin therapy inchronic HCV-1b infection using comprehensiveinformation of viral and host factors. (2010)
  • 著者名/発表者名: Maekawa S, Enomoto N, et al
  • 学会等名: 17^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • 発表場所: Yokohama
  • 年月日: 20100910-14
• [学会発表] Extensive analysis of serum cytokines associated to the response in the PEG-IFN+RBV combination therapy in genotype 1b HCV infection. (2010)
  • 著者名/発表者名: Kazuki Komase, Maekawa S, Enomoto N, et al
  • 学会等名: 17^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • 発表場所: Yokohama
  • 年月日: 20100910-14
• [学会発表] Investigation for viral genomic regions associated to hepatocarcinogenesis in hepatitis C. (2010)
  • 著者名/発表者名: Mika Miura, Maekawa S, Enomoto N, et al
  • 学会等名: 17^<th> International Meeting on Hepatitis C Virus and Related Viruses
  • 発表場所: Yokohama
  • 年月日: 20100910-14
• [学会発表] Analysis of the reaponse to pegylated-interferon plus ribavirin therapy in chronic HCV-1b infection using comprehensive information of viral and host factors. (2010)
  • 著者名/発表者名: Maekawa S, Enomoto N, et al
  • 学会等名: EASL(45th Annual meeting of the European association for the study of theliver) WIEN
  • 年月日: 2010-04-16
• [学会発表] Characterization of protease inhibitor resistance mutations in untreated patients infected with genotype 1b HCV. (2010)
  • 著者名/発表者名: Shindo H, Maekawa S, Enomoto N, et al
  • 学会等名: EASL(45th Annual meeting of the European association for the study of the liver) WIEN
  • 年月日: 2010-04-15