A large-scale genetic validation study coupled with in vitro analyses reveal a role for vitamin Dsignaling in the pathogenesis and response to treatment of hepatitis C virus infection

Détails

ID Serval
serval:BIB_A2865D1D58F3
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
A large-scale genetic validation study coupled with in vitro analyses reveal a role for vitamin Dsignaling in the pathogenesis and response to treatment of hepatitis C virus infection
Titre de la conférence
46th Annual Meeting of the European Association for the Study of the Liver (EASL)
Auteur(s)
Lange C.M., Bibert S., Kutalik Z., Morikawa K., Cerny A., Dufour J.F., Gerlach T.J., Heim M.H., Malinverni R., Muellhaupt B., Negro F., Badenhoop K., Sarrazin C., Berg T., Gouttenoire J., Bochud P.Y., Moradpour D.
Adresse
Berlin, Germany, March 30-April 3, 2011
ISBN
0168-8278
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
54
Série
Journal of Hepatology
Pages
S537
Langue
anglais
Notes
Publication type : Meeting Abstract
Résumé
Background and Aims: Vitamin D is an important modulatorof numerous cellular processes. Some of us recently observedan association of the 1a-hydroxylase promoter polymorphismCYP27B1-1260 rs10877012 with sustained virologic response (SVR)in a relatively small number of German patients with chronichepatitis C. In the present study, we aimed to validate thisassociation in a large and well characterized patient cohort, theSwiss Hepatitis C Cohort Study (SCCS). In addition, we examinedthe effect of vitamin D on the hepatitis C virus (HCV) life cyclein vitro.Methods: CYP27B1-1260 rs10877012 and IL28B rs12979860 singlenucleotide polymorphisms (SNPs) were genotyped in 1049 patientswith chronic hepatitis C from the SCCS, of whom 698 were treatedwith pegylated interferon-a (PEG-IFN-a) and ribavirin. In addition,112 patients with spontaneous clearance of HCV were examined.SNPs were correlated with variables reflecting the natural courseand treatment outcome of chronic hepatitis C. The effect of1,25-(OH)2D3 (calcitriol) on HCV replication and viral particleproduction was investigated in vitro using human hepatoma celllines (Huh-7.5) harbouring subgenomic replicons and cell culturederivedHCV.Results: The CYP27B1-1260 rs10877012 genotype was notassociated with SVR in patients with the good-response IL28Brs1279860 CC genotype. However, in patients with poor-responseIL28B rs1279860 genotype CT and TT, CYP27B1-1260 rs10877012was a significant independent predictor of SVR (15% difference inSVR between rs10877012 genotype AA vs. CC, p = 0.030, OR = 1.495,95% CI = 1.038-2.152). The CYPB27-1260 rs10877012 genotype wasneither associated with spontaneous clearance of HCV, nor withliver fibrosis progression rate, inflammatory activity of chronichepatitis C, or HCV viral load. Physiological doses of 1,25-(OH)2D3did not significantly affect HCVRNA replication or infectiousparticle production in vitro.Conclusions: The results of this large-scale genetic validationstudy reveal a role of vitamin D metabolism in the responseto treatment in chronic hepatitis C, but 1,25-(OH)2D3 does notexhibit a significant direct inhibitory antiviral effect. Thus, theability of vitamin D to modulate immunity against HCV shouldbe investigated.
Mots-clé
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Web of science
Création de la notice
03/01/2012 14:15
Dernière modification de la notice
20/08/2019 16:08
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