Association Of Promoter Polymorphisms Of Interferon-alpha Receptor-1 Gene With The Response To Interferon-alpha In Patients With Chronic Hepatitis B

ObjectiveThe aim of this study was to determine the association between promoter polymorphisms of interferon-alpha receptor-1 gene and the response to interferon-alpha in patients with chronic hepatitis B.Methods1. Sixty-one patients with chronic hepatitis B who received interferon-alpha(IFN-α)therapy participated in this study underwent HBV genotypes tests before treatment, and then they were treated with recombinant IFN-α2b by intramuscular injection at the dosage of 5 MU every other day for 48 weeks, then the responses to IFN-αwere observed.2. The interferon-alpha receptor-1(IFNAR1) gene promoter was sequenced in these patients.Results1. Among the Sixty-one patients treated with recombinant IFN-α2b, responsers were 30(49.180%), non responsers were 31(50.820%).There were no significant difference in sex, age, alanine aminotransferase(ALT)testing and HBVDNA level testing before treatment between the responsers and the non responsers, but the ratio of the number of HBV genotype B to the number of HBV genotype C was significant higher in the responsers than the non responsers, P=0.042.2. Three polymorphic sites were identified at loci -408, -3 and -77,and they were separately:-408C/T,-3C/T and -77 GT microsatellite repeat sequence(-77(GT)n).These three site were in linkage, and they composed some haplotypes, such as haplotype -408C一-77(GT)5一-3C.3. Response rate to IFN-αtherapy:Chronic hepatitis B patients with the genotype -408C一-77(GT)5一-3C/-408C一-77(GT)5一-3C or genotype -408C一-77(GT)5一-3C/non-408C一-77(GT)5一-3C in IFNAR1 gene promoter produced a higher response rate to IFN-αtherapy than those with genotype non-408C一-77(GT)5一-3C/ non-408C一-77(GT)5一-3C, 60.976% versus 25.000%,P=0.013.4. Negative conversion rate of HBsAg:Chronic hepatitis B patients with the genotype -408C一-77(GT)5一-3C/-408C一-77(GT)5一-3C in IFNAR1 gene promoter produced a higher negative conversion rate of HBsAg than the patients with genotype -408C一-77(GT)5一-3C/non-408C一-77(GT)5一-3C, 36.364% versus 6.667%,P=0.035.Conclusions1. The chronic hepatitis B patients with HBV genotype B have a better response to IFN-αthan the patients with HBV genotype C.2.The genotype -408C一-77(GT)5一-3C/-408C一-77(GT)5一-3C of the IFNAR1 prometer is associated with better response to IFN-αtreatment in patients with chronic hepatitis B, suggesting that promoter polymorphisms of IFNAR1 gene are associated with the response to IFN-αtreatment.