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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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.
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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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