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A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C
BACKGROUND: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. METHODOLOGY/PRINCIPAL FINDINGS: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxy...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395683/ https://www.ncbi.nlm.nih.gov/pubmed/22808108 http://dx.doi.org/10.1371/journal.pone.0040159 |
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author | Lange, Christian M. Bibert, Stephanie Kutalik, Zoltan Burgisser, Philippe Cerny, Andreas Dufour, Jean-Francois Geier, Andreas Gerlach, Tilman J. Heim, Markus H. Malinverni, Raffaele Negro, Francesco Regenass, Stephan Badenhoop, Klaus Bojunga, Jörg Sarrazin, Christoph Zeuzem, Stefan Müller, Tobias Berg, Thomas Bochud, Pierre-Yves Moradpour, Darius |
author_facet | Lange, Christian M. Bibert, Stephanie Kutalik, Zoltan Burgisser, Philippe Cerny, Andreas Dufour, Jean-Francois Geier, Andreas Gerlach, Tilman J. Heim, Markus H. Malinverni, Raffaele Negro, Francesco Regenass, Stephan Badenhoop, Klaus Bojunga, Jörg Sarrazin, Christoph Zeuzem, Stefan Müller, Tobias Berg, Thomas Bochud, Pierre-Yves Moradpour, Darius |
author_sort | Lange, Christian M. |
collection | PubMed |
description | BACKGROUND: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. METHODOLOGY/PRINCIPAL FINDINGS: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D(3) (25[OH]D(3)) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D(3)<20 ng/mL) during all seasons, but 25(OH)D(3) serum levels were not associated with treatment outcome. CONCLUSIONS/SIGNIFICANCE: Our study suggests a role of bioactive vitamin D (1,25[OH](2)D(3), calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D(3) is not a suitable predictor of treatment outcome. |
format | Online Article Text |
id | pubmed-3395683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33956832012-07-17 A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C Lange, Christian M. Bibert, Stephanie Kutalik, Zoltan Burgisser, Philippe Cerny, Andreas Dufour, Jean-Francois Geier, Andreas Gerlach, Tilman J. Heim, Markus H. Malinverni, Raffaele Negro, Francesco Regenass, Stephan Badenhoop, Klaus Bojunga, Jörg Sarrazin, Christoph Zeuzem, Stefan Müller, Tobias Berg, Thomas Bochud, Pierre-Yves Moradpour, Darius PLoS One Research Article BACKGROUND: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. METHODOLOGY/PRINCIPAL FINDINGS: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D(3) (25[OH]D(3)) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D(3)<20 ng/mL) during all seasons, but 25(OH)D(3) serum levels were not associated with treatment outcome. CONCLUSIONS/SIGNIFICANCE: Our study suggests a role of bioactive vitamin D (1,25[OH](2)D(3), calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D(3) is not a suitable predictor of treatment outcome. Public Library of Science 2012-07-12 /pmc/articles/PMC3395683/ /pubmed/22808108 http://dx.doi.org/10.1371/journal.pone.0040159 Text en Lange et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lange, Christian M. Bibert, Stephanie Kutalik, Zoltan Burgisser, Philippe Cerny, Andreas Dufour, Jean-Francois Geier, Andreas Gerlach, Tilman J. Heim, Markus H. Malinverni, Raffaele Negro, Francesco Regenass, Stephan Badenhoop, Klaus Bojunga, Jörg Sarrazin, Christoph Zeuzem, Stefan Müller, Tobias Berg, Thomas Bochud, Pierre-Yves Moradpour, Darius A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C |
title | A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C |
title_full | A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C |
title_fullStr | A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C |
title_full_unstemmed | A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C |
title_short | A Genetic Validation Study Reveals a Role of Vitamin D Metabolism in the Response to Interferon-Alfa-Based Therapy of Chronic Hepatitis C |
title_sort | genetic validation study reveals a role of vitamin d metabolism in the response to interferon-alfa-based therapy of chronic hepatitis c |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3395683/ https://www.ncbi.nlm.nih.gov/pubmed/22808108 http://dx.doi.org/10.1371/journal.pone.0040159 |
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