GNB3 C825T polymorphism and response to interferon-alfa/ribavirin treatment in patients with hepatitis C virus genotype 1 (HCV-1) infection

Background/Aims: The outcome of infection with the hepatitis C virus (HCV) has been shown to be influenced by genetic host factors. The G protein β3 subunit (GNB3) C825T polymorphism has been shown to determine immune cell functions in vitro. We investigated the association of GNB3 genotypes with treatment response in HCV-infected patients. Methods: We genotyped 1781 HCV-free blood donors and 232 HCV-infected patients treated with interferon-alfa/ ribavirin. Sustained virologic response (SVR) was defined by undetectable HCV-RNA 24 weeks after discontinuation of therapy. Non-response (NR) was defined by positive HCV-RNA at the end of at least 24 weeks of treatment. GNB3 genotypes were determined by DNA restriction enzyme analyses. Results: Genotype distribution was not significantly different in healthy controls and HCV-infected patients. Only in HCV genotype 1-infected patients a significant correlation between GNB3 CC genotype and NR could be observed (6 TT, 42 TC, 54 CC) versus SVR (11 TT, 25 TC, 19 CC) patients (P=0.004). In a logistic regression analysis including biochemical and virologic characteristics, only GNB3 CC genotype was significantly associated with NR (OR 4.9; 95% CI=1.4-16.5; P=0.011). Conclusions: The GNB3 825 CC genotype is associated with NR in HCV-1-infected patients.