CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection
Copyright policy )CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection
IL28B polymorphisms strongly predict spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. A recent study proposed a 32-base pair deletion in the CC-chemokine receptor 5 (CCR5) gene (CCR5-Δ32) interacting with the IL28B polymorphisms to influence spontaneous HCV clearance. The aim of this study was to clarify the role of CCR5-Δ32 in treatment-induced clearance of chronic hepatitis C (CHC). A cross-sectional cohort of 813 Caucasian patients with CHC genotype 1 (365 responders and 448 non-responders) who had received standard of care dual therapy with interferon (IFN)-α and ribavirin (RBV) was genotyped for the CCR5-Δ32 and IL28B polymorphisms to examine their interaction with respect to treatment response. CCR5-Δ32 did not influence treatment-induced recovery to IFN-α/RBV in CHC, and did not improve prediction of sustained virological response in the context of the IL28B polymorphisms in a multivariate model. CCR5-Δ32 homozygotes were significantly more frequent in those with CHC than healthy controls in the European cohorts (2.9% vs 0.4%, P<0.0001), but not in Australians of European ancestry. In conclusion, CCR5-Δ32 does not influence treatment response in the context of IL28B polymorphisms. Although CCR5-Δ32 may affect viral clearance within closely controlled geographical and genetic environments, we found no effect in larger cohorts treated with dual therapy.
- University of Turin Italy
- University of Bonn Germany
- Charité - University Medicine Berlin Germany
- UNSW Sydney Australia
- University of Nottingham United Kingdom
hepatitis C virus, Male, Genetic-variation, genotype, IL28B, 32 Biomedical and Clinical Sciences, Hepatitis, Cohort Studies, Single-source, Receptors, anzsrc-for: 1107 Immunology, Chronic, 3202 Clinical Sciences, IFN-α, Sequence Deletion, anzsrc-for: 3204 Immunology, Genome-wide association, Liver Disease, International Hepatitis C Genetics Consortium (IHCGC), 3 Good Health and Well Being, interferon, Single Nucleotide, Middle Aged, Prognosis, Hepatitis C, Europe, Infectious Diseases, Treatment Outcome, Combination, HCV, Chronic hepatitis-C, anzsrc-for: 3202 Clinical Sciences, Drug Therapy, Combination, Female, Infection, Adult, 2716 Genetics (clinical), SVR, Genotype, ribavirin, Chronic Liver Disease and Cirrhosis, 610, HIV-1 infection, Antiviral Agents, Polymorphism, Single Nucleotide, White People, anzsrc-for: 32 Biomedical and Clinical Sciences, genetic polymorphisms, 1311 Genetics, Hepatitis - C, Drug Therapy, Genetic, XXXXXX - Unknown, Ribavirin, 616, Genetics, Humans, Polymorphism, 2403 Immunology, Base Sequence, Interleukins, Australia, Interferon-alpha, Epistasis, Genetic, Hepatitis C, Chronic, Spontaneous clearance, anzsrc-for: 3105 Genetics, Emerging Infectious Diseases, Cross-Sectional Studies, Antiviral treatment, Mutation, Multivariate Analysis, Epistasis, Interferons, Digestive Diseases, CCR5, Chemokine receptor-5
hepatitis C virus, Male, Genetic-variation, genotype, IL28B, 32 Biomedical and Clinical Sciences, Hepatitis, Cohort Studies, Single-source, Receptors, anzsrc-for: 1107 Immunology, Chronic, 3202 Clinical Sciences, IFN-α, Sequence Deletion, anzsrc-for: 3204 Immunology, Genome-wide association, Liver Disease, International Hepatitis C Genetics Consortium (IHCGC), 3 Good Health and Well Being, interferon, Single Nucleotide, Middle Aged, Prognosis, Hepatitis C, Europe, Infectious Diseases, Treatment Outcome, Combination, HCV, Chronic hepatitis-C, anzsrc-for: 3202 Clinical Sciences, Drug Therapy, Combination, Female, Infection, Adult, 2716 Genetics (clinical), SVR, Genotype, ribavirin, Chronic Liver Disease and Cirrhosis, 610, HIV-1 infection, Antiviral Agents, Polymorphism, Single Nucleotide, White People, anzsrc-for: 32 Biomedical and Clinical Sciences, genetic polymorphisms, 1311 Genetics, Hepatitis - C, Drug Therapy, Genetic, XXXXXX - Unknown, Ribavirin, 616, Genetics, Humans, Polymorphism, 2403 Immunology, Base Sequence, Interleukins, Australia, Interferon-alpha, Epistasis, Genetic, Hepatitis C, Chronic, Spontaneous clearance, anzsrc-for: 3105 Genetics, Emerging Infectious Diseases, Cross-Sectional Studies, Antiviral treatment, Mutation, Multivariate Analysis, Epistasis, Interferons, Digestive Diseases, CCR5, Chemokine receptor-5
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