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The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients
BACKGROUND: The hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepat...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Kowsar
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908614/ https://www.ncbi.nlm.nih.gov/pubmed/27313635 http://dx.doi.org/10.5812/hepatmon.35597 |
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author | Bokharaei-Salim, Farah Salehi-Vaziri, Mostafa Sadeghi, Farzin Esghaei, Maryam Monavari, Seyed Hamidreza Alavian, Seyed Moayed Fakhim, Shahin Keyvani, Hossein |
author_facet | Bokharaei-Salim, Farah Salehi-Vaziri, Mostafa Sadeghi, Farzin Esghaei, Maryam Monavari, Seyed Hamidreza Alavian, Seyed Moayed Fakhim, Shahin Keyvani, Hossein |
author_sort | Bokharaei-Salim, Farah |
collection | PubMed |
description | BACKGROUND: The hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries. OBJECTIVES: The aim of this study was to investigate the association of substitutions in the HCV subtype 1b (HCV-1b) core protein and the rs12979860 polymorphism in the interleukin 28B gene (IL28B) with the response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients. PATIENTS AND METHODS: A total of fifty-one chronically HCV-1b-infected Azerbaijani patients were enrolled in this cross-sectional study from March 2010 to June 2015. After RNA extraction from pre-treatment plasma, the core region of the HCV genome was amplified using the nested reverse transcription (RT) polymerase chain reaction (PCR) method, followed by standard sequencing. In addition, genomic DNA was extracted from peripheral blood mononuclear cell (PBMC) specimens, and the rs12979860 single nucleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: In this study, a significant association was observed between the non-responders and relapsers to antiviral therapy and substitutions in the HCV-1b core region at positions 43 (R43K, P = 0.047), 70 (R70Q, P < 0.001), 91 (M91L, P = 0.037), and 106 (S106N, P = 0.018). Concerning the IL28B polymorphism, the results showed that sustained virological response was significantly associated with homozygous CC patients (P = 0.009) as compared with other genotypes, while homozygous TT subjects were associated with HCV relapse after therapy (P = 0.006). CONCLUSIONS: The data of the present study suggest that amino acid substitutions at position 43, 70, 91, and 106 in the HCV-1b core protein are correlated with the response to the Peg-IFNα-2a/RBV treatment in Azerbaijani patients with chronic hepatitis C. Moreover, host genetic polymorphisms, such as those of the IL28B locus, might be useful for predicting the responsiveness to Peg-IFNα-2a/RBV combination therapy against HCV. |
format | Online Article Text |
id | pubmed-4908614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Kowsar |
record_format | MEDLINE/PubMed |
spelling | pubmed-49086142016-06-16 The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients Bokharaei-Salim, Farah Salehi-Vaziri, Mostafa Sadeghi, Farzin Esghaei, Maryam Monavari, Seyed Hamidreza Alavian, Seyed Moayed Fakhim, Shahin Keyvani, Hossein Hepat Mon Research Article BACKGROUND: The hepatitis C virus (HCV) infection has been identified as a leading cause of progressive liver diseases worldwide. Despite new treatment strategies, pegylated interferon alfa-2a (Peg-IFNα-2a), in combination with ribavirin (RBV), still represents the gold standard of therapy for hepatitis C in developing countries. OBJECTIVES: The aim of this study was to investigate the association of substitutions in the HCV subtype 1b (HCV-1b) core protein and the rs12979860 polymorphism in the interleukin 28B gene (IL28B) with the response to Peg-IFNα-2a/RBV combination therapy in Azerbaijani patients. PATIENTS AND METHODS: A total of fifty-one chronically HCV-1b-infected Azerbaijani patients were enrolled in this cross-sectional study from March 2010 to June 2015. After RNA extraction from pre-treatment plasma, the core region of the HCV genome was amplified using the nested reverse transcription (RT) polymerase chain reaction (PCR) method, followed by standard sequencing. In addition, genomic DNA was extracted from peripheral blood mononuclear cell (PBMC) specimens, and the rs12979860 single nucleotide polymorphism (SNP) was identified using a PCR-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: In this study, a significant association was observed between the non-responders and relapsers to antiviral therapy and substitutions in the HCV-1b core region at positions 43 (R43K, P = 0.047), 70 (R70Q, P < 0.001), 91 (M91L, P = 0.037), and 106 (S106N, P = 0.018). Concerning the IL28B polymorphism, the results showed that sustained virological response was significantly associated with homozygous CC patients (P = 0.009) as compared with other genotypes, while homozygous TT subjects were associated with HCV relapse after therapy (P = 0.006). CONCLUSIONS: The data of the present study suggest that amino acid substitutions at position 43, 70, 91, and 106 in the HCV-1b core protein are correlated with the response to the Peg-IFNα-2a/RBV treatment in Azerbaijani patients with chronic hepatitis C. Moreover, host genetic polymorphisms, such as those of the IL28B locus, might be useful for predicting the responsiveness to Peg-IFNα-2a/RBV combination therapy against HCV. Kowsar 2016-04-23 /pmc/articles/PMC4908614/ /pubmed/27313635 http://dx.doi.org/10.5812/hepatmon.35597 Text en Copyright © 2016, Kowsar Corp http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. |
spellingShingle | Research Article Bokharaei-Salim, Farah Salehi-Vaziri, Mostafa Sadeghi, Farzin Esghaei, Maryam Monavari, Seyed Hamidreza Alavian, Seyed Moayed Fakhim, Shahin Keyvani, Hossein The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients |
title | The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients |
title_full | The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients |
title_fullStr | The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients |
title_full_unstemmed | The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients |
title_short | The Association of Substitutions in the Hepatitis C Virus Subtype 1b Core Gene and IL28B Polymorphisms With the Response to Peg-IFNα-2a/RBV Combination Therapy in Azerbaijani Patients |
title_sort | association of substitutions in the hepatitis c virus subtype 1b core gene and il28b polymorphisms with the response to peg-ifnα-2a/rbv combination therapy in azerbaijani patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908614/ https://www.ncbi.nlm.nih.gov/pubmed/27313635 http://dx.doi.org/10.5812/hepatmon.35597 |
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