2010 Fiscal Year Final Research Report
Association of gene expression involving innate immunity and genetic variation in IL28B with antiviral response
| Project/Area Number |
20590769
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
ASAHINA Yasuhiro University of Yamanashi, 大学院・医学工学総合研究部, 医学研究員 (00422692)
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| Co-Investigator(Kenkyū-buntansha) |
IZUMI Namiki 山梨大学, 大学院・医学工学総合研究部, 医学研究員 (20397300)
KUROSAKI Masayuki 山梨大学, 大学院・医学工学総合研究部, 医学研究員 (10280976)
ENOMOTO Nobuyuki 山梨大学, 大学院・医学工学総合研究部, 教授 (20251530)
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| Project Period (FY) |
2008 – 2010
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| Keywords | C型肝炎 / 自然免疫 / RIG-1 / IPS-1 / IL28B / インターフェロン / リバビリン / テラプレビル |
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| Research Abstract |
Innate immunity plays an important role in host antiviral response to hepatitis C viral (HCV) infection. Recently, single nucleotide polymorphism (SNP) of IL28B and host response to pegylated interferon・(PEG-IFN・)and ribavirin (RBV) were shown to be strongly associated. We aimed to determine the gene expression involving innate immunity in IL28B genotypes and elucidate its relation to response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFN・-2b/RBV and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and USP18), and IL28 (IFN・). Both IL28B SNPs were 100% identical ; 54 patients possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral sensors and modulators in IL28B minor patients were significantly up-regulated compared with that in IL28B major patients (~3.3 fold, p<0.001). However, expression of IPS-1 was significantly lower in IL28B minor patients (1.2 fold, p=0.028). Hepatic expressions of viral sensors and modulators were significantly higher in non-virological responders (NVR) than that in others despite stratification by IL28B genotype (~2. 6 fold, p<0.001). Multivariate and ROC analyses indicated that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were independent factors for NVR. Conclusion : Gene expression involving innate immunity is strongly associated with IL28B genotype and response to PEG-IFN・/RBV. Both IL28B minor allele and higher RIG-land ISG15 expressions and RIG-I/IPS-1 ratio are independent factors for NVR.
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[Journal Article] A predictive model of response to peginterferon ribavirin in chronic hepatitis C using classification and regression tree analysis.2010
Author(s)
Kurosaki M, Matsunaga K, Hirayama T, Tanaka T, Sato M, Yasui Y, Tamaki N, Hosokawa T, Leda K, Tsuchi ya K, Nakanishi H, Ikeda H, Itakura J, Takahashi Y, Asahina Y Higaki M, Enomoto N, Izumi N
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Journal Title
Hepatol Res 40
Pages: 251-260
Peer Reviewed
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[Journal Article] Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection.2010
Author(s)
Asahina Y, Tsuchiya K, Tamaki N, Hirayama T, Tanaka T, Sato M, Yasui Y, Hosokawa T, Ueda K, Kuzuya T, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N Izumi N
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Journal Title
Hepatology 52
Pages: 518-527
Peer Reviewed
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[Journal Article] Hepatic steatosis in chronic hepatitis C is a significant risk factor for developing hepatocellular carcinoma independent of age, sex, obesity, fibrosis stage and response to interferon therapy.2010
Author(s)
Kurosaki M, Ilosokawa T, Matsunaga K, Iirayama I, Tanaka T, Sato M, Yasui Y, Tamaki N, Ueda K, Tsuchiya K, KuzuyaT, Nakanishi H, Itakura J, Takahashi Y, Asahina Y, Enomoto N, Izumi N
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Journal Title
Hepatol Res 40
Pages: 870-877
Peer Reviewed
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[Journal Article] The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy.2008
Author(s)
Kurosaki M, Matsunaga K, Hirayama I, Tanaka T, Sato M, Komatsu N, Umeda N, Ilosokawa T, Ueda K, Tsuchiya K, Nakanishi it, Itakura J, Asahina Y, Miyake S, Enomoto N Izumi N
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Journal Title
J Hepatol 48
Pages: 736-742
Peer Reviewed
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[Journal Article] Potential relevance of cytoplasmic viral sensors and related regulators involving innate immunity in antiviral response.2008
Author(s)
Asahina Y, Izumi N, Hirayama I, Tanaka T, Sato M, Yasui Y, Komatsu N, Umeda N, Hosokawa T, Leda K, Tsuchiya K, Nakanishi H, Itakura J, Kurosaki M, Enomoto N, Tasaka M, Sakamoto N, Miyake S
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Journal Title
Gastroenterology 134
Pages: 1396-1405
Peer Reviewed
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[Presentation] Gene expression involving innate immunity and IL28B variation: its association with antiviral response in chronic hepatitis C.2010
Author(s)
Asahina Y, Tanaka K, Suzuki Y, Tamaki N, Hoshioka T, Katoh T, Tanaka T, Yasui Y, Hosokawa T, Leda K, Kuzuya T, Tsuchiya K, Nakanishi II, Itakura J Takahashi Y, Kurosaki M, Izumi N.
Organizer
The 61st Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2010)
Place of Presentation
Boston, USA
Year and Date
2010-10-30
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[Presentation] Association between gene expression involving innate immunity and genetic variation in IL28B in antiviral treatment response.2010
Author(s)
Asahina Y, Suzuki Y, Tamaki N, Kato T, Yasui Y, Hosokawa T, Ueda K, Kuzuya T, Tsuchiya K, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Izumi N
Organizer
17th International Meeting on Hepatitis C Virus and Related Viruses (HCV 2010)
Place of Presentation
Tokyo
Year and Date
2010-09-11
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[Presentation] Dynamic response of innate immunity induced by telaprevir and PEG-IFN/RBV treatment and its association with virological response and HCV variants.2009
Author(s)
Asahina Y, Hirayama I, Tamaki N, Yasui Y, Tanaka T, Sato M, Ueda K, Kuzuya T, Tsuchiya K, Nakanishi H, Itakura J, Kurosaki M, Izumi N
Organizer
The 60th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2009)
Place of Presentation
Boston, USA
Year and Date
2009-10-31
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[Presentation] Gene expression involving innate immunity and hepatitis C virus mutation in resistance to peginterferon alfa-2b plus ribavirin treatment.2008
Author(s)
Asahina Y, Hirayam I, Tanaka T, Sato M, Yasui Y, Tamaki N, Umeda N, Hosokawa T, Ueda K, Ikeda H, Tsuchiya K, Nakanishi H, Itakura, Kurosaki M, Maekawa S, Enomoto M, Izumi N
Organizer
The 59th Annual Meeting of the American Association for the Study of Liver Disease (AASLD The Liver Meeting 2008)
Place of Presentation
San Francisco, USA
Year and Date
2008-10-31
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