CCR5-Delta32 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-Delta32) interacting with the IL28B polymorphisms to influence spontaneous HCV clearance. The aim of this study was to clarify the role of CCR5-Delta32 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)-alpha and ribavirin (RBV) was genotyped for the CCR5-Delta32 and IL28B polymorphisms to examine their interaction with respect to treatment response. CCR5-Delta32 did not influence treatment-induced recovery to IFN-alpha/RBV in CHC, and did not improve prediction of sustained virological response in the context of the IL28B polymorphisms in a multivariate model. CCR5-Delta32 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-Delta32 does not influence treatment response in the context of IL28B polymorphisms. Although CCR5-Delta32 may affect viral clearance within closely controlled geographical and genetic environments, we found no effect in larger cohorts treated with dual therapy.
|ISBN||1476-5470 (Electronic) 1466-4879 (Linking)|
|Authors||Suppiah, V.; Armstrong, N. J.; 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.;|
|Publisher Name||GENES AND IMMUNITY|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12154|