Influence of interleukin 12B (IL12B) polymorphisms on spontaneous and treatment-induced recovery from hepatitis C virus infection

Background/Aims: Interleukin-12 (IL-12) governs the Th1-type immune response, affecting the spontaneous and treatment-induced recovery from HCV-infection. We investigated whether the IL12B polymorphisms within the promoter region (4 bp insertion/deletion) and the 3(')-UTR (1188-A/C), which have been reported to influence IL-12 synthesis, are associated with the outcome of HCV infection. Methods: We analyzed 186 individuals with spontaneous HCV clearance, 501 chronically HCV infected patients, and 217 healthy controls. IL12B 3'-UTR and promoter genotyping was performed by Taqman-based assays with allele-specific oligonucleotide probes and PCR-based allele-specific DNA-amplification, respectively. Results: The proportion of IL12B promoter and 3'-UTR genotypes did not differ significantly between the different cohorts. However, HCV genotype I-infected patients with high baseline viremia carrying the IL12B 3'-UTR 1188-C-allele showed significantly higher sustained virologic response (SVR) rates (25.3% vs. 46% vs. 54.5% for A/A, A/C and C/C) due to reduced relapse rates (24.2% vs. 12% vs. zero % for A/A, A/C and C/C). Conclusions: IL12B 3'-UTR 1188-C-allele carriers appear to be capable of responding more efficiently to antiviral combination therapy as a consequence of a reduced relapse rate. No association of IL12B polymorphisms and selflimited HCV infection could be demonstrated. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.