IL-28BのSNPとHCV遺伝子に関する研究

2011 年度 研究成果報告書

• 研究課題/領域番号: 22790646
• 研究種目: 若手研究(B)
• 配分区分: 補助金
• 研究分野: 消化器内科学
• 研究機関: 広島大学
• 研究代表者: 阿部 弘美 広島大学, 大学院・医歯薬学総合研究科, 特任助教 (70572329)
• 研究期間 (年度): 2010 – 2011
• キーワード: 肝臓学 / ヒトゲノム / ウイルス / ヒト肝細胞キメラマウス

研究概要

慢性C型肝炎患者に対する治療薬はペグインターフェロン・リバビリン併用療法が主なものである。近年慢性C型肝炎に対する治療抵抗性を規定するSNPがIL-28B遺伝子内に存在することが報告された。本研究では患者肝生検サンプルを用いて治療前の肝内インターフェロン関連遺伝子の発現状態を調べ、IL-28BのSNPが著効例に多いタイプでは抗ウイルス遺伝子の発現が低く、インターフェロンシグナルを負に制御する遺伝子の発現が高いことを報告した。

研究成果

• [雑誌論文] IL28B polymorphism is associated with fatty change in the liver of chronichepatitis 1 C patients (2012)
  • 著者名/発表者名: Ohnishi M, Tsuge M, Kohno T, Zhang Y, Abe H, Hyogo H, Kimura Y, Miki D, Hiraga N, Imamura M, Takahashi S, Ochi H, Hayes CN, Tanaka S, Arihiro K, Chayama K
  • 雑誌名: J Gastroenterol. In press
• [雑誌論文] Severe Necroinflammatory Reaction Caused by Natural Killer By Fas/ FasLInteraction and Dendritic Cells in Human Hepatocyte Chimeric Mouse (2012)
  • 著者名/発表者名: Okazaki A, Hiraga N, Imamura M, Hayes CN, Tsuge M, Takahashi S, Aikata H, Abe H, Miki D, Ochi H, TatenoC, Yoshizato K, Ohdan H, Chayama K
  • 雑誌名: Hepatology. In press
• [雑誌論文] Serum PAI-1 is a novel predictor for response to pegylated interferon-α-2bplus ribavirin therapy in chronichepatitis C virus infection (2012)
  • 著者名/発表者名: Miki D, Ohishi W, Ochi H, Hayes CN, Abe H, Tsuge M, Imamura M, KamataniN, Nakamura Y, Chayama K
  • 雑誌名: J Viral Hepat 巻: 19 ページ: 126-133
• [雑誌論文] Toward the establishment of aprediction system for the personalized treatment of chronic hepatitis C (2012)
  • 著者名/発表者名: Ochi H, Hayes CN, Abe H, Hayashida Y, Uchiyama T, Kamatani N, Nakamura Y, Chayama K
  • 雑誌名: J Infect Dis 巻: 205 ページ: 204-210
• [雑誌論文] Hepatitis C virus in fection suppresses the interferon response in the liver of thehuman hepatocyte chimeric mouse (2011)
  • 著者名/発表者名: Tsuge M, Fujimoto Y, Hiraga N, Zhang Y, Ohnishi M, Kohno T, Abe H, Miki D, Imamura M, Takahashi S, Ochi H, HayesCN, Miya F, Tsunoda T, Chayama K
  • 雑誌名: PLoS One 巻: 6
• [雑誌論文] A Genome-Wide Association Study of Chronic Hepatitis B Identified Novel Risk Locus in a Japanese Population (2011)
  • 著者名/発表者名: Mbarek H, Ochi H, Urabe Y, Kumar V, Kubo M, Hosono N, Takahashi A, Kamatani Y, Miki D, Abe H, Tsunoda T, Kamatani N, Chayama K, Nakamura Y, Matsuda K
  • 雑誌名: Hum Mol Genet 巻: 20 ページ: 3884-3892
• [雑誌論文] Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers (2011)
  • 著者名/発表者名: Miki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, Ikeda K, KumadaH, Toyota J, Morizono T, Tsunoda T, Kubo M, Nakamura Y, Kamatani N, Chayama KMiki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, Ikeda K, KumadaH, Toyota J, Morizono T, Tsunoda T, M, Nakamura Y, Kamatani N, Chayama K
  • 雑誌名: Nat Genet 巻: 43 ページ: 797-800
• [雑誌論文] Effects of hepatitis B virus in fection on the interferon response in immunodeficient human hepatocyte chimeric mice (2011)
  • 著者名/発表者名: Tsuge M, Takahashi S, Hiraga N, Fujimoto Y, Zhang Y, Mitsui F, Abe H, Kawaoka T, Imamura M, Ochi H, HayesCN, Chayama K
  • 雑誌名: J Infect Dis 巻: 204 ページ: 224-228
• [雑誌論文] IL28B But Not ITPA Polymorphism Is Predictive of Response to Pegylated Interferon, Ribavirin, and Telaprevir Triple Therapy in Patients With Genotype 1 Hepatitis C (2011)
  • 著者名/発表者名: Chayama K, Hayes CN, Abe H, Miki D, Ochi H, Karino Y, Toyota J, Nakamura Y, Kamatani N, Sezaki H, Kobayashi M, Akuta N, Suzuki F, Kumada H
  • 雑誌名: J Infect Dis 巻: 204 ページ: 84-93
• [雑誌論文] Rapid emergence of telaprevir resistant hepatitis C virus strain fromwild type clone in vivo (2011)
  • 著者名/発表者名: Hiraga N, Imamura M, Abe H, NelsonHayes C, Kono T, Onishi M, Tsuge M, Takahashi S, Ochi H, Iwao E, Kamiya N, Yamada I, Tateno C, Yoshizato K, MatsuiH, Kanai A, Inaba T, Tanaka S, Chayama K
  • 雑誌名: Hepatology 巻: 54 ページ: 781-788
• [雑誌論文] Impact of viral amino acid substitutions and host IL28B polymorphism on replication and susceptibility to interferon of hepatitis Cvirus (2011)
  • 著者名/発表者名: Hiraga N, Abe H, Imamura M, Tsuge M, Takahashi S, Hayes CN, Ochi H, TatenoC, Yoshizato K, Nakamura Y, KamataniN, Chayama K
  • 雑誌名: Hepatology 巻: 54 ページ: 764-771
• [雑誌論文] Inverse association of IL28 Bgenotype and liver mRNA expression of genes promoting or suppressing antiviralstate (2011)
  • 著者名/発表者名: Abe H, Hayes C. N, Ochi H, Tsuge M, Miki D, Hiraga N, Imamura M, Takahashi S, Kubo M, Nakamura Y, Kamatani N, Chayama K
  • 雑誌名: J Med. Virol 巻: 83 ページ: 1597-1607
• [雑誌論文] Common genetic polymorphism of ITPA gene affects ribavirin-inducedanemia and effect of peg-interferon plusribavirin therapy (2011)
  • 著者名/発表者名: Azakami T, Hayes CN, Sezaki H, Kobayashi M, Akuta N, Suzuki F, Kumada H, Abe H, Miki D, Tsuge M, Imamura M, Kawakami Y, Takahashi S, Ochi H, Nakamura Y, Kamatani N, Chayama K
  • 雑誌名: J Med. Virol 巻: 83 ページ: 1048-1057
• [雑誌論文] Prediction of response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infectedwith hepatitis C virus genotype 1b (2011)
  • 著者名/発表者名: Hashimoto Y, Ochi H, Abe H, HayashidaY, Tsuge M, Mitsui F, Hiraga N, Imamura M, Takahashi S, Nelson HayesC, Ohishi W, Kubo M, Tsunoda T, Kamatani N, Nakamura Y, Chayama K
  • 雑誌名: J Med. Virol 巻: 83 ページ: 981-988
• [雑誌論文] IL-28B predicts response to chronichepatitis C therapy-fine-mapping andreplication study in Asian populations (2011)
  • 著者名/発表者名: Ochi H, Maekawa T, Abe H, Hayashida Y, Nakano R, Imamura M, Hiraga N, Kawakami Y, Aimitsu S, Kao JH, KuboM, Tsunoda T, Kumada H, Nakamura Y, Hayes CN, Chayama K
  • 雑誌名: J Gen Virol 巻: 92 ページ: 1091-1081
• [雑誌論文] Animal model for study of human hepatitis viruses (2011)
  • 著者名/発表者名: Chayama K, Hayes CN, Hiraga N, Abe H, Tsuge M, Imamura M
  • 雑誌名: J Gastroenterol Hepatol 巻: 26 ページ: 13-18
• [雑誌論文] Amino acid substitutions in core and NS5A regions of the HCV genome canpredict virological decrease withpegylated interferon plus ribavirin therapy (2011)
  • 著者名/発表者名: Kitamura S, Tsuge M, Hatakeyama T, Abe H, Imamura M, Mori N, Saneto H, Kawaoka T, Mitsui F, Hiraga N, Takaki S, Kawakami Y, Aikata H, Takahashi S, Ohishi W, Ochi H, Hayes CN, Chayama K
  • 雑誌名: Antivir Ther 巻: 15 ページ: 1087-1097
• [雑誌論文] ME3738 enhances the effect of interferon and inhibits hepatitis C virusreplication both in vitro and in vivo (2011)
  • 著者名/発表者名: Abe H, Imamura M, Hiraga N, Tsuge M, Mitsui F, Kawaoka T, Takahashi S, OchiH, Maekawa T, Hayes CN, Tateno C, Yoshizato K, Murakami S, Yamashita N, Matsuhira T, Asai K, Chayama K
  • 雑誌名: J Hepatol 巻: 55 ページ: 11-18
• [雑誌論文] Elimination of hepatitis C virus byshort term NS3-4A and NS5B inhibitorcombination the rapy in human hepatocyte chimeric mice (2011)
  • 著者名/発表者名: Ohara E, Hiraga N, Imamura M, Iwao E, Kamiya N, Yamada I, Kono T, Onishi M, Hirata D, Mitsui F, Kawaoka T, Tsuge M, Takahashi S, Abe H, Hayes CN, Ochi H, Tateno C, Yoshizato K, Tanaka S, Chayama K
  • 雑誌名: J Hepatol 巻: 54 ページ: 872-878
• [雑誌論文] IL28 variation affects expression of interferon stimulated genes andpeg-interferon and ribavirin therapy (2011)
  • 著者名/発表者名: Abe H, Hayes CN, Ochi H, Maekawa T, Tsuge M, Miki D, Mitsui F, Hiraga N, Imamura M, Takahashi S, Kubo M, Nakamura Y, Chayama K
  • 雑誌名: J Hepatol 巻: 54 ページ: 1094-1101
• [雑誌論文] A single nucleotide polymorphism in activated cdc42 associated tyrosine kinase 1 influences the interferon therapy in hepatitis C patients (2011)
  • 著者名/発表者名: Fujimoto Y, Ochi H, Maekawa T, Abe H, Hayes CN, Kumada H, Nakamura Y, Chayama K
  • 雑誌名: J Hepatol 巻: 54 ページ: 629-639
• [雑誌論文] Predictive value of the IL28 Bpolymorphism on the effect of interferontherapy in chronic hepatitis C patientswith genotypes 2a and 2b (2011)
  • 著者名/発表者名: Kawaoka T, Hayes CN, Ohishi W, Ochi H, Maekawa T, Abe H, Tsuge M, Mitsui F, Hiraga N, Imamura M, Takahashi S, Kubo M, Tsunoda T, Nakamura Y, Kumada H, Chayama K
  • 雑誌名: J Hepatol 巻: 54 ページ: 408-414
• [雑誌論文] HCV substitutions and IL28B polymor phisms on out come of peg-interferon plus ribavirin combination the rapy (2011)
  • 著者名/発表者名: Hayes CN, Kobayashi M, Akuta N, Suzuki F, Kumada H, Abe H, Miki D, Imamura M, Ochi H, Kamatani N, Nakamura Y, Chayama K
  • 雑誌名: Gut 巻: 60 ページ: 261-267
• [雑誌論文] ITPA polymorphism affectsribavirin-induced anemia and outcomes of the rapy-a genome-wide study ofJapanese HCV virus patients (2010)
  • 著者名/発表者名: Ochi H, Maekawa T, Abe H, Hayashida Y, Nakano R, Kubo M, Tsunoda T, HayesCN, Kumada H, Nakamura Y, Chayama K
  • 雑誌名: Gastroenterology 巻: 139 ページ: 1190-1197
• [雑誌論文] Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitisC virus patients (2010)
  • 著者名/発表者名: Abe H, Ochi H, Maekawa T, Hayes CN, Tsuge M, Miki D, Mitsui F, Hiraga N, Imamura M, Takahashi S, Ohishi W, Arihiro K, Kubo M, Nakamura Y, Chayama K
  • 雑誌名: J Hepatol 巻: 53 ページ: 439-443
• [雑誌論文] Importance of serum concentration of adefovir for Lamivudine-adefovircombination therapy in patients withlamivudine-resistant chronic hepatitis (2010)
  • 著者名/発表者名: B. Mitsui F, Tsuge M, Kimura T, KitamuraS, Abe H, Saneto H, Kawaoka T, Miki D, Hatakeyama T, Hiraga N, Imamura M, Kawakami Y, Aikata H, Takahashi S, Hayes CN, Igarashi H, Morimoto K, Shimizu M, Chayama K
  • 雑誌名: Antimicrob Agents Chemother 巻: 54 ページ: 3205-3211
• [雑誌論文] Differential effects of interferon and lamivudine on serum HBV RNAinhibition in patients with chronichepatitisB (2010)
  • 著者名/発表者名: Huang YW, Chayama K, Tsuge M, Takahashi S, Hatakeyama T, Abe H, HuJT, Liu CJ, Lai MY, Chen DS, Yang SS, Kao JH
  • 雑誌名: Antivir Ther 巻: 15 ページ: 177-184
• [雑誌論文] HBx protein is in dispensable for development of viraemia in humanhepatocyte chimeric mice (2010)
  • 著者名/発表者名: Tsuge M, Hiraga N, Akiyama R, TanakaS, Matsushita M, Mitsui F, Abe H, Kitamura S, Hatakeyama T, Kimura T, Miki D, Mori N, Imamura M, TakahashiS, Hayes CN, Chayama K
  • 雑誌名: J Gen Virol 巻: 91 ページ: 1854-1864
• [雑誌論文] G to A hypermutation of TT virus (2010)
  • 著者名/発表者名: Tsuge M, Noguchi C, Akiyama R, Matsushita M, Kunihiro K, Tanaka S, Abe H, Mitsui F, Kitamura S, Hatakeyama T, Kimura T, Miki D, Hiraga N, Imamura M, Takahashi S, Hayses CN, Chayama K.
• [学会発表] IL28Bの遺伝子多型とその他の調節機構による抗ウイルス遺伝子と抑制性遺伝子の間の反対方向の調節 (2011)
  • 著者名/発表者名: 阿部弘美
  • 学会等名: 日本肝臓学会
  • 発表場所: 東京
  • 年月日: 20110602-03
• [学会発表] Pretreatment of hepatomacell lines with IL28B delaysinterferon-induced ISG expression, whereas pretreatment with neutralizingan tibodies against IL28B reduces ISG expression levels (2011)
  • 著者名/発表者名: Abe H. et al
  • 学会等名: 46th Annual Meeting ofEuropean Association for the Study of theLiver(EASL)
  • 発表場所: Berlin, Germany
  • 年月日: 20110330-0403
• [学会発表] Reciprocal control of interferon stimulated gene mRNAs betweenpositive anti-viral effecter and negativeregulator by IL28B gene polymorphism andby another regulatory mechanism (2010)
  • 著者名/発表者名: Abe H. et al
  • 学会等名: AASLDAnnual Meeting
  • 発表場所: Boston, USA
  • 年月日: 20101029-1102
• [備考]
  • URL: http://home.hiroshima-u.ac.jp/naika1/
• [備考]
  • URL: http://home.hiroshima-u.ac.jp/nbard/biom/saisei.htm
• [備考]
  • URL: http://www.src.riken.go.jp/group/liver/index.html