GNB3 C825T polymorphism and response to interferon-alfa/ribavirin treatment in patients with hepatitis C virus genotype 1 (HCV-1) infection.
OBJECTIVE
The outcome of infection with the hepatitis C virus (HCV) has been shown to be influenced by genetic host factors. The G protein beta3 subunit (GNB3) C825T polymorphism has been shown to determine immune cell functions in vitro. We investigated the association of GNB3 genotypes with treatment response in HCV-infected patients.


METHODS
We genotyped 1781 HCV-free blood donors and 232 HCV-infected patients treated with interferon-alfa/ribavirin. Sustained virologic response (SVR) was defined by undetectable HCV-RNA 24 weeks after discontinuation of therapy. Non-response (NR) was defined by positive HCV-RNA at the end of at least 24 weeks of treatment. GNB3 genotypes were determined by DNA restriction enzyme analyses.


RESULTS
Genotype distribution was not significantly different in healthy controls and HCV-infected patients. Only in HCV genotype 1-infected patients a significant correlation between GNB3 CC genotype and NR could be observed (6 TT, 42 TC, 54 CC) versus SVR (11 TT, 25 TC, 19 CC) patients (P = 0.004). In a logistic regression analysis including biochemical and virologic characteristics, only GNB3 CC genotype was significantly associated with NR (OR 4.9; 95% CI = 1.4-16.5; P = 0.011).


CONCLUSIONS
The GNB3 825 CC genotype is associated with NR in HCV-1-infected patients.
Sarrazin
Christoph
C
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Kirrberger Str. 41, D-66421 Homburg/Saar, Germany.
Berg
Thomas
T
Weich
Viola
V
Mueller
Tobias
T
Frey
Ulrich H
UH
Zeuzem
Stefan
S
Gerken
Guido
G
Roggendorf
Michael
M
Siffert
Winfried
W
D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006526:Hepatitis C / Q000188:drug therapy* / Q000635:transmission; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D015819:Substance Abuse, Intravenous; D019562:Viral Load
D000998:Antiviral Agents; C454420:G-protein beta3 subunit; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D021122:Protein Subunits; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D020962:Heterotrimeric GTP-Binding Proteins