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CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection

Lookup NU author(s): Professor Margaret Bassendine, Dr David Sheridan, Jaime Jonsson

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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


Publication metadata

Author(s): Suppiah V, Armstrong NJ, O'Connor KS, Berg T, Weltman M, Abate ML, Spengler U, Bassendine M, Dore GJ, Irving WL, Powell E, Nattermann J, Mueller T, Riordan S, Stewart GJ, George J, Booth DR, Ahlenstiel G, Michalk M, Malik B, McClure P, Smith S, Sheridan D, Snape E, Fragomeli V, Norris R, How-Chow D, Jonsson JR, Barrie H, Stelzer-Braid S, Fletcher S, Applegate T, Grebely J, Matthews G, Bharadwaj M, Smedile A, the International Hepatitis C Genetics Consortium (IHCGC)

Publication type: Article

Publication status: Published

Journal: Genes and Immunity

Year: 2013

Volume: 14

Issue: 5

Pages: 286-290

Print publication date: 01/07/2013

ISSN (print): 1466-4879

ISSN (electronic): 1476-5470

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/gene.2013.15

DOI: 10.1038/gene.2013.15

PubMed id: 23594959


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