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Association of genetic variations in GNB1 with response to peginterferon plus ribavirin therapy for chronic hepatitis C in a Chinese population in Taiwan.

ABSTRACT: The aim of this study was to evaluate whether polymorphisms in the guanine nucleotide binding (G protein), beta polypeptide 1 (GNB1) gene are associated with a rapid virological response (RVR) among HCV genotype 1 (HCV-1) and 2 (HCV-2) infected patients receiving peginterferon plus ribavirin treatment (PEG-IFN?-RBV).We analyzed the association between RVR to PEG-IFN?-RBV therapy and 4 tagging single nucleotide polymorphisms (SNPs) of the GNB1 gene. This study included 265 HCV-1 and 195 HCV-2 infected patients in a Chinese population in Taiwan.Among the GNB1 SNPs examined, the combination of genotypes G/G and G/T populations of rs12126768 was significant inversely correlated with RVR in HCV-1 infected patients (P = 0.0330), whereas HCV-2 infected patients, combination of A/A and A/C genotypes populations at rs4648727 responded better to the PEG-IFN?-RBV treatment (P = 0.0089). However, there were no significant differences in the allele frequencies of those SNPs between RVR responders and non-responders. Several RVR susceptibility GNB1 haplotypes were identified, and the ACAT haplotype of the 4 SNPs may increase the successful outcomes of HCV-1 and HCV-2 infected patients (P = 0.0261 and P = 0.0253, respectively).The data for GNB1 SNPs and the association of RVR showed that GNB1 polymorphisms might be associated with the therapeutic outcomes of HCV-1 and HCV-2 infected patients under standard of care (SOC) treatment.

SUBMITTER: Lim YP

PROVIDER: S-EPMC3536692 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Association of genetic variations in GNB1 with response to peginterferon plus ribavirin therapy for chronic hepatitis C in a Chinese population in Taiwan.

Lim Yun-Ping YP Tsai Fuu-Jen FJ Liao Wen-Ling WL Tien Ni N Hung Dong-Zong DZ Peng Cheng-Yuan CY Wan Lei L

BMC gastroenterology 20121122

<h4>Background</h4>The aim of this study was to evaluate whether polymorphisms in the guanine nucleotide binding (G protein), beta polypeptide 1 (GNB1) gene are associated with a rapid virological response (RVR) among HCV genotype 1 (HCV-1) and 2 (HCV-2) infected patients receiving peginterferon plus ribavirin treatment (PEG-IFNα-RBV).<h4>Methods</h4>We analyzed the association between RVR to PEG-IFNα-RBV therapy and 4 tagging single nucleotide polymorphisms (SNPs) of the GNB1 gene. This study i ...[more]

PMID: 23171003

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Project description:AIM:To evaluate addition of boceprevir to peginterferon/ribavirin (PR) in Russian patients with chronic hepatitis C virus (HCV). METHODS:Treatment-naive (TN) and treatment-experienced (TE) patients (who had failed prior treatment with PR for ? 12 wk) with chronic HCV genotype 1 infection were enrolled in this placebo-controlled, double-blind study. All patients initially received PR for 4 wk. Patients randomized to control treatment then received PR for an additional 44 wk. TN patients randomized to triple therapy received boceprevir (800 mg three times daily) plus PR for 24 wk and then further therapy according to treatment week 8 (TW8) HCV RNA levels. TE patients received boceprevir plus PR for 32 wk and then further therapy according to TW8 HCV RNA levels. Treatment was discontinued for TN patients with detectable HCV RNA at TW24 and TE patients with detectable HCV RNA at TW12 because of futility. The primary efficacy end point was sustained virologic response (SVR) defined as undetectable HCV RNA 24 wk after completing all study therapy. RESULTS:SVR was 74.8% in the boceprevir plus PR arm compared with 46.2% in the control arm, with a stratification-adjusted treatment difference of 29.2% (95%CI: 16.4-41.5; P < 0.0001). Rates of SVR were higher in the boceprevir arm in both TN and TE patient groups (TN 78.4% vs 56.3%; TE 69.4% vs 30.0%). Within TE patients, the rates of SVR were higher with boceprevir plus PR compared with PR, regardless of treatment failure type (null responder, partial responder, and relapser). Most patients receiving boceprevir plus PR in both TN (86%) and TE (71%) populations were eligible for reduced treatment duration. Anemia was increased in patients receiving boceprevir plus PR vs PR alone (47.2% vs 24.4%); there was a corresponding increase in ribavirin dose reduction and erythropoietin use. Among patients receiving boceprevir plus PR, SVR rates were similar in patients with anemia (< 10 g/dL) and those without anemia (71.2% vs 77.4%). CONCLUSION:Regulatory approval has been obtained for boceprevir plus PR in Russian patients with HCV genotype 1 infection based on the results of this study.

Project description:This study investigates differences in depression and anxiety between patients with chronic hepatitis C who are treated with peginterferon alpha-2a (PegIFN-?-2a) plus ribavirin and those who are treated with peginterferon alpha-2b (PegIFN-?-2b) plus ribavirin.In this 24 week, non-randomized, observational, prospective study, 55 patients with chronic hepatitis C were treated with PegIFN-?-2a plus ribavirin (Group 1), and 26 patients were treated with PegIFN-?-2b plus ribavirin (Group 2). All patients underwent assessment using the Hospital Anxiety and Depression Scale (HADS) at the baseline and at weeks 4, 12 and 24. Patients with depression scores (HADS-D)???8 and anxiety scores (HADS-A)???8 were defined as having depression and anxiety, respectively. The factors that were associated with depression and anxiety during the 24 week antiviral treatment were determined.During the 24 week antiviral treatment, the proportion of patients with depression significantly increased over time in both groups (Group 1: p?=?0.048; Group 2: p?=?0.044). The proportion of patients with anxiety did not significantly change during the follow-up period in either group. Incidences of depression or anxiety did not differ significantly between Group 1 and Group 2. A history of alcohol use disorder was an independent predictor of depression at week 12 (p?<?0.001) and week 24 (p?<?0.001), and a poor virological response to treatment was associated with depression at week 24 (p?=?0.029). Patients who had more physical comorbidities were more likely to suffer from anxiety at week 12 (p?=?0.038).This study did not identify significant differences in depression or anxiety between in patients with chronic hepatitis C who underwent a 24 week antiviral treatment regimen with PegIFN-?-2a plus ribavirin and those who underwent a regiment with PegIFN-?-2b plus ribavirin. Future research with larger samples and a randomized, controlled design are required to verify the findings in this study.This clinical study has been registered at ClinicalTrials.gov. (Trial registration: NCT02943330 ).

Dataset Information

Association of genetic variations in GNB1 with response to peginterferon plus ribavirin therapy for chronic hepatitis C in a Chinese population in Taiwan.

Publications

Association of genetic variations in GNB1 with response to peginterferon plus ribavirin therapy for chronic hepatitis C in a Chinese population in Taiwan.

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