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Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection

Melissa E. Laird 1 Amira Mohsen 2 Darragh Duffy 1 Rasha Mamdouh 3 Lenaig Lefouler 4 Armanda Casrouge 1 Mai El-Daly 5 Mona Rafik 3 Mohamed Mohamed 6, 5 Alexandre Soulier 7, 8 Jean-Michel Pawlotsky 8, 7 Christophe Hézode 7, 9 Isabelle Rosa 7, 9 Philippe Renard 10 Mostafa K. Mohamed 5 Philippe Bonnard 11 Jacques Izopet 12 Vincent Mallet 13, 14 Stanislas Pol 13, 14 Matthew L. Albert 1, 13, * Arnaud Fontanet 4, *
* Corresponding author
1 Immunobiologie des Cellules Dendritiques
2 Community Medicine Department
3 Faculty of medicine
4 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
5 liver diseases research unit
6 Minia University
7 IMRB - Institut Mondor de Recherche Biomédicale
8 CNR for Viral Hepatitis B, C, and D
9 Service d'hépato-gastro-entérologie [APHP Henri Mondor]
10 Department of gastroenterology and hepatology
11 Service des maladies infectieuses et tropicales [CHU Tenon]
12 Laboratoire de Virologie
13 Service d'hépatologie médicale [CHU Cochin]
14 IC UM3 (UMR 8104 / U1016) - Institut Cochin
Abstract : BACKGROUND & AIMS: HCV requires host lipid metabolism for replication, and apolipoproteins have been implicated in the response to treatment. METHODS: We examined plasma apolipoprotein concentrations in three cohorts of patients: mono-infected patients with symptomatic acute hepatitis C (aHCV); those undergoing treatment for chronic hepatitis C (cHCV); and HIV/HCV co-infected patients being treated for their chronic hepatitis C. We also evaluated associations between apolipoproteins and IL28B polymorphisms, a defined genetic determinant of viral clearance. RESULTS: Plasma apolipoprotein H (ApoH) levels were significantly higher in patients who achieved spontaneous clearance or responded to pegylated-interferon/ribavirin therapy. Strikingly, patients carrying the IL28B rs12979860 CC SNP correlated with the plasma concentration of ApoH in all three cohorts. Both ApoH and IL28B CC SNP were associated with HCV clearance in univariate analysis. Additional multivariate analysis revealed that the association between IL28B and HCV clearance was closely linked to that of Apo H and HCV clearance, suggesting that both belong to the same biological pathway to clearance. The association between IL28B CC SNP and ApoH was not observed in healthy individuals, suggesting that early post-infection events trigger differential ApoH expression in an IL28B allele dependent manner. CONCLUSIONS: This relationship identifies ApoH as the first induced protein quantitative trait associated with IL28B, and characterises a novel host factor implicated in HCV clearance
Keywords : Hepatitis C virus Quantitative trait loci Lipid metabolism Apolipoproteins IL28B
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01384212
Contributor : Marie-Christine Vougny <>
Submitted on : Wednesday, October 19, 2016 - 3:24:57 PM
Last modification on : Monday, June 14, 2021 - 4:24:03 PM

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PASTEUR | CNRS | CNAM | UPMC | IMRB | ATP-IMMUN | UPEC-UPEM | UNIV-PARIS5 | USPC | UNIV-HESAM | SORBONNE-UNIVERSITE | SU-MEDECINE | UPEC | UNIV-PARIS | UP-SANTE

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Melissa E. Laird, Amira Mohsen, Darragh Duffy, Rasha Mamdouh, Lenaig Lefouler, et al.. Apolipoprotein H expression is associated with IL28B genotype and viral clearance in hepatitis C virus infection. Journal of Hepatology, Elsevier, 2014, 61 (4), pp.770 - 776. ⟨10.1016/j.jhep.2014.05.040⟩. ⟨pasteur-01384212⟩

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