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-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 D3 (25[OH]D3) 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]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome.

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Author:Christian LangeGND, Stephanie Bibert, Zoltán Kutalik, Philippe Burgisser, Andreas Cerny, Jean-Francois Dufour, Andreas Geier, Tilman J. Gerlach, Markus H. Heim, Raffaele Malinverni, Francesco Negro, Stephan Regenass, Klaus BadenhoopORCiDGND, Jörg BojungaGND, Christoph SarrazinGND, Stefan ZeuzemORCiDGND, Tobias Müller, Thomas BergORCiDGND, Pierre-Yves Bochud, Darius Moradpour
URN:urn:nbn:de:hebis:30:3-257656
DOI:https://doi.org/10.1371/journal.pone.0040159
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/22808108
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2012/07/12
Date of first Publication:2012/07/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Creating Corporation:Swiss Hepatitis C Cohort Study Group
Release Date:2012/08/15
Volume:7
Issue:(7):e40159
Page Number:8
HeBIS-PPN:357941403
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0