Polymorphisms in the interferon-γ gene at position +874 in patients with chronic hepatitis C treated with high-dose interferon-α and ribavirin

Abstract

To investigate the influence of the T-to-A polymorphic sequence at position +874 in the interferon (IFN)-γ gene (+874 IFN-γ) on the response to combination therapy with high-dose interferon and ribavirin, the single nucleotide polymorphisms were determined by using a polymerase chain reaction sequence-specific primers approach in 150 histologically proved chronic hepatitis C (CHC) patients. The distribution of genotypes for +874 IFN-γ were T/T: 6 (4.0%), T/A: 31 (20.7%) and A/A: 113 (75.3%) and 24.7% (37/150) of patients were inherited T allele. After undergoing combination therapy with high-dose IFN-α and ribavirin, 70.7% (106/150) of patients achieved sustained viral response (SVR). Based on multivariate regression analyses, the independent factors predicting HCV SVR after combination therapy were HCV genotype non-1b ( P < 0.001) and low pretreatment HCV RNA levels ( P = 0.041) (odds ratios/95% C.I.: 10.150/4.023–25.609 and 0.581/0.345–0.979, respectively). No association between genotypes, A or T alleles of +874 IFN-γ and response to combination therapy with high-dose IFN-α and ribavirin. In conclusion, we found that with high SVR rates after combination therapy with high-dose IFN-α and ribavirin, HCV genotypes and pretreatment serum HCV RNA levels, but not inheritance of the IFN-γ polymorphism at the position +847, were predictors for SVR.