| Mutations in carboxy-terminal part of E2 including PKR/eIF2α phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b： Their correlation with response to interferon monotherapy and viral load |
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| 引用本文： | Ukai K,Ishigami M,Yoshioka K,Kawabe N,Katano Y,Hayashi K,Honda T,Yano M,Goto H. Mutations in carboxy-terminal part of E2 including PKR/eIF2α phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b： Their correlation with response to interferon monotherapy and viral load[J]. World journal of gastroenterology : WJG, 2006, 12(23): 3722-3728. DOI: 10.3748/wjg.v12.i23.3722 |
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| 作者姓名： | Ukai K Ishigami M Yoshioka K Kawabe N Katano Y Hayashi K Honda T Yano M Goto H |
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| 摘 要： |
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| 关 键 词： | 基因突变 羧基端子 磷酸化作用 干扰素 丙型肝炎病毒 |
| 收稿时间： | 2006-01-25 |
Mutations in carboxy-terminal part of E2 including PKR/eIF2alpha phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b: their correlation with response to interferon monotherapy and viral load |
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| Ukai Koji,Ishigami Masatoshi,Yoshioka Kentaro,Kawabe Naoto,Katano Yoshiaki,Hayashi Kazuhiko,Honda Takashi,Yano Motoyoshi,Goto Hidemi. Mutations in carboxy-terminal part of E2 including PKR/eIF2alpha phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b: their correlation with response to interferon monotherapy and viral load[J]. World journal of gastroenterology : WJG, 2006, 12(23): 3722-3728. DOI: 10.3748/wjg.v12.i23.3722 |
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| Authors: | Ukai Koji Ishigami Masatoshi Yoshioka Kentaro Kawabe Naoto Katano Yoshiaki Hayashi Kazuhiko Honda Takashi Yano Motoyoshi Goto Hidemi |
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| Affiliation: | Division of Liver and Biliary Diseases, Department of Internal Medicine, Fujita Health University School of Medicine, Kutsukake, Toyoake, Aichi, Japan. |
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| Abstract: | AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-1b-infected patients treated with IFN. METHODS: The C-terminal part of E2 (codons 617-711) including PKR/eIF2alpha phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to IFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to IFN (25.0% vs 6.9%, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P < 0.0001) and sustained response to IFN (85.7% vs 2.9%, P < 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P < 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independent predictors for small viral load, and ISDR (OR = 39.0, P < 0.0001) was selected as the only independent predictor for sustained response. CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load. |
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| Keywords: | E2 Genotype HCV Interferon ISDR NS5A PePHD PKR SVR |
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