Relationship between the genetic variation in interleukin 28B and response to antiviral therapy in patients with chronic hepatitis C.

BACKGROUND: Genetic variations at the interleukin 28B (IL-28B) locus are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. The aim of this research was to evaluate the role of IL-28B single nucleotide polymorphism (SNP) variations in Chinese patients undergoing pegylated interferon-α plus ribavirin (PEG-IFN-α/RBV) treatment. METHODS: To determine the effect of IL-28B variation on the response to HCV therapy, these variants were genotyped in a cohort of 220 patients who were chronically infected with HCV and received combined PEG-IFN-α/RBV therapy. RESULTS: The proportions of rs12979860 CC, CT, and TT genotypes were 71.4%, 25.0%, and 3.6% respectively, in the sustained virological response (SVR) group; 15.8%, 60.5%, and 23.7% respectively, in the null virological response (NVR) group; and 38.1%, 52.4%, and 9.5% respectively, in the relapse (Rel) group (P < 0.05). Logistic regression analysis showed that, compared to those having the CC genotype, CT heterozygotes had an increased risk of NVR and Rel (OR = 10.95, 95%CI = 4.12-29.11, P = 1.5×10(-7) and OR = 3.93, 95%CI = 1.86-8.32, P = 2.1×10(-4) respectively). The RNA quantification assay showed that patients with genotype CC exhibited much higher levels of IL-28 expression than those with genotype CT or TT (P < 0.001). CONCLUSIONS: The IL-28B SNP rs12979860 genotype was related to the effectiveness of HCV therapy: patients with the CC rs12979860 genotype had higher rates of SVR than those with the CT or TT genotype, and the CC genotype revealed a significantly higher level of IL-28 mRNA expression.