CCR5 Promoter Polymorphism Influences the Interferon Response of Patients with Chronic Hepatitis C in Japan

Abstract

Objective: Chemokines and chemokine receptors play important roles in the pathogenesis of chronic hepatitis C. Here, we explore the influence of genetic polymorphisms of chemokine and chemokine receptors such as regulated upon activation and T cell secreted (RANTES), CC chemokine receptor 5 (CCR5) and CCR2 on the outcome of interferon (IFN) monotherapy. Methods: In a cohort of 105 patients with chronic hepatitis C as well as in 50 sustained responders and 55 nonresponders the presence of polymorphisms such as CCR5-Δ32, CCR5 59029G/A, CCR2 V64I and RANTES –403G/C was determined. Results: Gender, age, liver histological staging, pretreatment ALT levels, total dose of IFN and frequencies of polymorphisms (CCR2 V64I and RANTES –403G/C) did not significantly differ between the two groups. A low viral load, hepatitis C virus (HCV) serotype 2 and CCR5 59029G/G were significantly associated with a higher probability of a sustained response (p < 0.01, p < 0.05, p < 0.05, respectively). Multiple logistic regression analysis showed that a low viral load, HCV serotype 2 and CCR5 59029G/G were independently associated with a sustained response [odds ratio 3.980 (1.647–9.621), p = 0.002; 3.584 (1.439–8.924), p = 0.006; 3.638 (1.163–11.379), p = 0.026, respectively]. Conclusion: These findings indicate that CCR5 59029 is a host genetic factor that is associated with responses to IFN therapy among Japanese patients with chronic hepatitis C.