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

Suppiah, V., Armstrong, N.J.ORCID: 0000-0002-4477-293X, O'Connor, K.S., Berg, T., Weltman, M., Abate, M.L., Spengler, U., Bassendine, M., Dore, G.J., Irving, W.L., Powell, E., Nattermann, J., Mueller, T., Riordan, S., Stewart, G.J., George, J., Booth, D.R., Ahlenstiel, G., Michalk, M., Malik, B., McClure, P., Smith, S., Sheridan, D., Snape, E., Fragomeli, V., Norris, R., How-Chow, D., Jonsson, J.R., Barrie, H., Stelzer-Braid, S., Fletcher, S., Applegate, T., Grebely, J., Matthews, G., Bharadwaj, M. and Smedile, A. (2013) CCR5-Δ32 genotype does not improve predictive value of IL28B polymorphisms for treatment response in chronic HCV infection. Genes and Immunity, 14 (5). pp. 286-290.

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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.

Item Type: Journal Article
Publisher: Nature Publishing Group
Copyright: © 2013 Macmillan Publishers Limited
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