Analysis of the relationship between IL28B SNP and HCV genome

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790646
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Hiroshima University
• Principal Investigator: ABE Hiromi 広島大学, 大学院・医歯薬学総合研究科, 特任助教 (70572329)
• Project Period (FY): 2010 – 2011
• Keywords: 肝臓学 / ヒトゲノム / ウイルス / ヒト肝細胞キメラマウス

Research Abstract

The current standard treatment for patients chronically infected with HCV is the combination of peg-interferon(PEG-IFN) and ribavirin(RBV). It has been reported that genetic variations within IL28B gene are associated with the effect of the PEG-IFN and RBV combination therapy. In this study, we investigated the expression levels of interferon related genes in the liver using liver biopsy from HCV patients before the treatment. We reported that the expression levels of anti-viral genes are lower, but those of negative regulator in IFN signaling are higher in favorable IL28B genotype patients.

Research Products

• [Journal Article] IL28B polymorphism is associated with fatty change in the liver of chronichepatitis 1 C patients (2012)
  • Author(s): 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
  • Journal Title: J Gastroenterol. In press
• [Journal Article] Severe Necroinflammatory Reaction Caused by Natural Killer By Fas/ FasLInteraction and Dendritic Cells in Human Hepatocyte Chimeric Mouse (2012)
  • Author(s): 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
  • Journal Title: Hepatology. In press
• [Journal Article] Serum PAI-1 is a novel predictor for response to pegylated interferon-α-2bplus ribavirin therapy in chronichepatitis C virus infection (2012)
  • Author(s): Miki D, Ohishi W, Ochi H, Hayes CN, Abe H, Tsuge M, Imamura M, KamataniN, Nakamura Y, Chayama K
  • Journal Title: J Viral Hepat Volume: 19 Pages: 126-133
• [Journal Article] Toward the establishment of aprediction system for the personalized treatment of chronic hepatitis C (2012)
  • Author(s): Ochi H, Hayes CN, Abe H, Hayashida Y, Uchiyama T, Kamatani N, Nakamura Y, Chayama K
  • Journal Title: J Infect Dis Volume: 205 Pages: 204-210
• [Journal Article] Hepatitis C virus in fection suppresses the interferon response in the liver of thehuman hepatocyte chimeric mouse (2011)
  • Author(s): 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
  • Journal Title: PLoS One Volume: 6
• [Journal Article] A Genome-Wide Association Study of Chronic Hepatitis B Identified Novel Risk Locus in a Japanese Population (2011)
  • Author(s): 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
  • Journal Title: Hum Mol Genet Volume: 20 Pages: 3884-3892
• [Journal Article] Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers (2011)
  • Author(s): 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
  • Journal Title: Nat Genet Volume: 43 Pages: 797-800
• [Journal Article] Effects of hepatitis B virus in fection on the interferon response in immunodeficient human hepatocyte chimeric mice (2011)
  • Author(s): Tsuge M, Takahashi S, Hiraga N, Fujimoto Y, Zhang Y, Mitsui F, Abe H, Kawaoka T, Imamura M, Ochi H, HayesCN, Chayama K
  • Journal Title: J Infect Dis Volume: 204 Pages: 224-228
• [Journal Article] 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)
  • Author(s): 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
  • Journal Title: J Infect Dis Volume: 204 Pages: 84-93
• [Journal Article] Rapid emergence of telaprevir resistant hepatitis C virus strain fromwild type clone in vivo (2011)
  • Author(s): 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
  • Journal Title: Hepatology Volume: 54 Pages: 781-788
• [Journal Article] Impact of viral amino acid substitutions and host IL28B polymorphism on replication and susceptibility to interferon of hepatitis Cvirus (2011)
  • Author(s): Hiraga N, Abe H, Imamura M, Tsuge M, Takahashi S, Hayes CN, Ochi H, TatenoC, Yoshizato K, Nakamura Y, KamataniN, Chayama K
  • Journal Title: Hepatology Volume: 54 Pages: 764-771
• [Journal Article] Inverse association of IL28 Bgenotype and liver mRNA expression of genes promoting or suppressing antiviralstate (2011)
  • Author(s): 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
  • Journal Title: J Med. Virol Volume: 83 Pages: 1597-1607
• [Journal Article] Common genetic polymorphism of ITPA gene affects ribavirin-inducedanemia and effect of peg-interferon plusribavirin therapy (2011)
  • Author(s): 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
  • Journal Title: J Med. Virol Volume: 83 Pages: 1048-1057
• [Journal Article] Prediction of response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infectedwith hepatitis C virus genotype 1b (2011)
  • Author(s): 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
  • Journal Title: J Med. Virol Volume: 83 Pages: 981-988
• [Journal Article] IL-28B predicts response to chronichepatitis C therapy-fine-mapping andreplication study in Asian populations (2011)
  • Author(s): 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
  • Journal Title: J Gen Virol Volume: 92 Pages: 1091-1081
• [Journal Article] Animal model for study of human hepatitis viruses (2011)
  • Author(s): Chayama K, Hayes CN, Hiraga N, Abe H, Tsuge M, Imamura M
  • Journal Title: J Gastroenterol Hepatol Volume: 26 Pages: 13-18
• [Journal Article] Amino acid substitutions in core and NS5A regions of the HCV genome canpredict virological decrease withpegylated interferon plus ribavirin therapy (2011)
  • Author(s): 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
  • Journal Title: Antivir Ther Volume: 15 Pages: 1087-1097
• [Journal Article] ME3738 enhances the effect of interferon and inhibits hepatitis C virusreplication both in vitro and in vivo (2011)
  • Author(s): 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
  • Journal Title: J Hepatol Volume: 55 Pages: 11-18
• [Journal Article] Elimination of hepatitis C virus byshort term NS3-4A and NS5B inhibitorcombination the rapy in human hepatocyte chimeric mice (2011)
  • Author(s): 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
  • Journal Title: J Hepatol Volume: 54 Pages: 872-878
• [Journal Article] IL28 variation affects expression of interferon stimulated genes andpeg-interferon and ribavirin therapy (2011)
  • Author(s): 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
  • Journal Title: J Hepatol Volume: 54 Pages: 1094-1101
• [Journal Article] A single nucleotide polymorphism in activated cdc42 associated tyrosine kinase 1 influences the interferon therapy in hepatitis C patients (2011)
  • Author(s): Fujimoto Y, Ochi H, Maekawa T, Abe H, Hayes CN, Kumada H, Nakamura Y, Chayama K
  • Journal Title: J Hepatol Volume: 54 Pages: 629-639
• [Journal Article] Predictive value of the IL28 Bpolymorphism on the effect of interferontherapy in chronic hepatitis C patientswith genotypes 2a and 2b (2011)
  • Author(s): 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
  • Journal Title: J Hepatol Volume: 54 Pages: 408-414
• [Journal Article] HCV substitutions and IL28B polymor phisms on out come of peg-interferon plus ribavirin combination the rapy (2011)
  • Author(s): Hayes CN, Kobayashi M, Akuta N, Suzuki F, Kumada H, Abe H, Miki D, Imamura M, Ochi H, Kamatani N, Nakamura Y, Chayama K
  • Journal Title: Gut Volume: 60 Pages: 261-267
• [Journal Article] ITPA polymorphism affectsribavirin-induced anemia and outcomes of the rapy-a genome-wide study ofJapanese HCV virus patients (2010)
  • Author(s): Ochi H, Maekawa T, Abe H, Hayashida Y, Nakano R, Kubo M, Tsunoda T, HayesCN, Kumada H, Nakamura Y, Chayama K
  • Journal Title: Gastroenterology Volume: 139 Pages: 1190-1197
• [Journal Article] Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitisC virus patients (2010)
  • Author(s): 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
  • Journal Title: J Hepatol Volume: 53 Pages: 439-443
• [Journal Article] Importance of serum concentration of adefovir for Lamivudine-adefovircombination therapy in patients withlamivudine-resistant chronic hepatitis (2010)
  • Author(s): 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
  • Journal Title: Antimicrob Agents Chemother Volume: 54 Pages: 3205-3211
• [Journal Article] Differential effects of interferon and lamivudine on serum HBV RNAinhibition in patients with chronichepatitisB (2010)
  • Author(s): Huang YW, Chayama K, Tsuge M, Takahashi S, Hatakeyama T, Abe H, HuJT, Liu CJ, Lai MY, Chen DS, Yang SS, Kao JH
  • Journal Title: Antivir Ther Volume: 15 Pages: 177-184
• [Journal Article] HBx protein is in dispensable for development of viraemia in humanhepatocyte chimeric mice (2010)
  • Author(s): 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
  • Journal Title: J Gen Virol Volume: 91 Pages: 1854-1864
• [Journal Article] G to A hypermutation of TT virus (2010)
  • Author(s): 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.
• [Presentation] 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)
  • Author(s): 阿部弘美
  • Organizer: 日本肝臓学会
  • Place of Presentation: 東京
  • Year and Date: 20110602-03
• [Presentation] Pretreatment of hepatomacell lines with IL28B delaysinterferon-induced ISG expression, whereas pretreatment with neutralizingan tibodies against IL28B reduces ISG expression levels (2011)
  • Author(s): Abe H. et al
  • Organizer: 46th Annual Meeting ofEuropean Association for the Study of theLiver(EASL)
  • Place of Presentation: Berlin, Germany
  • Year and Date: 20110330-0403
• [Presentation] Reciprocal control of interferon stimulated gene mRNAs betweenpositive anti-viral effecter and negativeregulator by IL28B gene polymorphism andby another regulatory mechanism (2010)
  • Author(s): Abe H. et al
  • Organizer: AASLDAnnual Meeting
  • Place of Presentation: Boston, USA
  • Year and Date: 20101029-1102
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/naika1/
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/nbard/biom/saisei.htm
• [Remarks]
  • URL: http://www.src.riken.go.jp/group/liver/index.html