title: CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection.
abstract: 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.
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute, University of Sydney, Sydney, NSW, Australia.
authors.forename: V
authors.initials: V
authors.lastname: Suppiah
authors.forename: N J
authors.initials: NJ
authors.lastname: Armstrong
authors.forename: K S
authors.initials: KS
authors.lastname: O'Connor
authors.forename: T
authors.initials: T
authors.lastname: Berg
authors.forename: M
authors.initials: M
authors.lastname: Weltman
authors.forename: M L
authors.initials: ML
authors.lastname: Abate
authors.forename: U
authors.initials: U
authors.lastname: Spengler
authors.forename: M
authors.initials: M
authors.lastname: Bassendine
authors.forename: G J
authors.initials: GJ
authors.lastname: Dore
authors.forename: W L
authors.initials: WL
authors.lastname: Irving
authors.forename: E
authors.initials: E
authors.lastname: Powell
authors.forename: J
authors.initials: J
authors.lastname: Nattermann
authors.forename: T
authors.initials: T
authors.lastname: Mueller
authors.forename: S
authors.initials: S
authors.lastname: Riordan
authors.forename: G J
authors.initials: GJ
authors.lastname: Stewart
authors.forename: J
authors.initials: J
authors.lastname: George
authors.forename: D R
authors.initials: DR
authors.lastname: Booth
authors.forename: G
authors.initials: G
authors.lastname: Ahlenstiel
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001315:Australia; D001483:Base Sequence; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D004843:Epistasis, Genetic; D005060:Europe; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019713:Receptors, CCR5 / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use; D017384:Sequence Deletion; D016896:Treatment Outcome; D044465:White People / Q000235:genetics; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D019713:Receptors, CCR5; D012254:Ribavirin; C584933:CCR5 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda