CCR5 promoter polymorphism influences the interferon response of patients with chronic hepatitis C in Japan.
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-Delta32, 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].


CONCLUSIONS
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.
Konishi
Ichiro
I
Third Department of Internal Medicine, Ehime University School of Medicine, Ehime, Japan.
Horiike
Norio
N
Hiasa
Yoichi
Y
Michitaka
Kojiro
K
Onji
Morikazu
M
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D012044:Regression Analysis; D012703:Serotyping; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; C515334:CCR2 protein, human; D018946:Chemokine CCL5; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D007372:Interferons