title: Polymorphisms in the interferon-gamma gene at position +874 in patients with chronic hepatitis C treated with high-dose interferon-alpha and ribavirin.
abstract: To investigate the influence of the T-to-A polymorphic sequence at position +874 in the interferon (IFN)-gamma gene (+874 IFN-gamma) 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-gamma 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-alpha 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-gamma and response to combination therapy with high-dose IFN-alpha and ribavirin. In conclusion, we found that with high SVR rates after combination therapy with high-dose IFN-alpha and ribavirin, HCV genotypes and pretreatment serum HCV RNA levels, but not inheritance of the IFN-gamma polymorphism at the position +847, were predictors for SVR.
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Chun-Ho Hospital, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Dai
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Chang
authors.forename: Shinn-Cherng
authors.initials: SC
authors.lastname: Chen
authors.forename: Li-Po
authors.initials: LP
authors.lastname: Lee
authors.forename: Ming-Yen
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Nei-Jen
authors.initials: NJ
authors.lastname: Hou
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Ming-Yuh
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Liang-Yen
authors.initials: LY
authors.lastname: Wang
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012254:Ribavirin / Q000008:administration & dosage*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; D007371:Interferon-gamma