Replicated Association Between an IL28B Gene Variant and a Sustained Response to Pegylated Interferon and Ribavirin

McCarthy, Jeanette; Li, Josephine H.; Thompson, Alexander; Suchindran, Sunil; Lao, Xiang Qian; Patel, Keyur; Tillmann, Hans L.; Muir, Andrew J.; McHutchison, John G.

doi:10.1053/j.gastro.2010.02.009

Cited by 299 publications

(344 citation statements)

References 21 publications

Supporting

Mentioning

273

Contrasting

Unclassified

Order By: Relevance

“…Two studies that were conducted in Western populations showed its relevance to Caucasians with HCV-2/HCV-3 infection, but the sample size was relatively small, and the results were inconsistent. 14,16 McCarthy et al 16 noted that there was no difference in effect of rs12979860, a novel SNP that determines 14 showed that the discriminatory power of rs8099917 to identify likely responders to treatment was restricted to HCV-1 patients and did not apply to HCV-2 patients. Our results have demonstrated that the effect of SNP rs8099917 in the context of other variables is confined to early viral kinetics and does not apply to antiviral therapy outcomes in HCV-2 patients.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15][16]33 In addition, SNPs have also been shown to be associated with the spontaneous clearance of HCV infection. 14,34 Subjects enrolled in genetic association studies were mostly infected with HCV-1, however.…”

Section: Discussionmentioning

confidence: 99%

“…Previous genome-wide association studies have indicated that SNPs rs12979860 and rs8099917 are related to treatment outcomes for Caucasians and African Americans with HCV-1 infection. [13][14][15][16] On the other hand, rs12980275, rs11881222, rs7248668, rs8105790, rs8099917, rs4803219, and rs10853728 have been noted to be associated with antiviral treatment responses on the basis of genome-wide association studies and a replication study in patients of Asian ethnicity. 12 Because the minor allele frequencies of rs12980275, rs11881222, and rs7248668 are all less than 1% in Taiwanese, 19 rs8105790, rs8099917, rs4803219, and rs10853728 were selected as candidate SNPs in the present study.…”

Section: Methodsmentioning

confidence: 99%

“…[12][13][14][15] The linkage of the genetic variants to the on-treatment and posttreatment responses of HCV-2 patients has not been well investigated; there have been discordant results regarding its role in treatment outcomes in recent studies using Caucasian populations. 14,16 In the current study, therefore, we aimed to elucidate the role of IL-28B polymorphisms in the treatment response with respect to viral kinetics in a large Chinese cohort residing in Taiwan with HCV-2 infection.…”

Section: Role Of Interleukin-28b Polymorphisms In the Treatment Of Hementioning

confidence: 99%

See 3 more Smart Citations

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

et al. 2011

View full text Add to dashboard Cite

Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r 2 5 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P 5 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) 5 4.27, 95% confidence interval (CI) 5 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR 5 0.28, 95% CI 5 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR 5 3.10, 95% CI 5 1.34-7.21, P 5 0.008), and the pretreatment level of aspartate aminotransferase (OR 5 0.996, 95% CI 5 0.99-1.00, P 5 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI 5 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. Conclusion: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. (HEPATOLOGY 2011;53:7-13)

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Role Of Interleukin-28b Polymorphisms In the Treatment Of Hementioning

confidence: 99%

See 2 more Smart Citations

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

et al. 2011

View full text Add to dashboard Cite

show abstract

“…[9][10][11] The key roles of the cytokines in the pathogenesis and the self-limiting of HCV infection are becoming clearer. Tumor necrosis factor-α (TNF-α), one of the most important Th1 cytokines, exhibits a wide range of biological properties, including polarization of a Th1 response, immune response to infectious agents, and direct antiviral effects, is important in the host defense against viruses.…”

Section: Introductionmentioning

confidence: 99%

Tumor Necrosis Factor-α Promoter Gene Polymorphisms Are Not Associated with Hepatitis C Virus Infection in Chinese Hemodialysis Patients

Zhang

Zhu

et al. 2011

Renal Failure

View full text Add to dashboard Cite

Background and aims: The aim of this study was to investigate the possible influence of tumor necrosis factor-α (TNF-α) gene promoter polymorphisms on the hepatitis C virus (HCV) infection in Chinese hemodialysis (HD) patients. Methods: A total of 884 HD patients from 14 HD centers in south China were investigated. The TNF-α gene promoter polymorphisms at positions 238 and 308 of the patients were detected by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. Results: Among the 884 patients, 176 (19.9%) were anti-HCV (+), and 142 (80.7%) of the anti-HCV (+) patients became chronically infected. The anti-HCV (+) patients showed longer duration of HD, higher rate of blood transfusion, kidney transplantation, and dialyzer reuse, compared with the anti-HCV (−) patients. However, the distributions of TNF-α −238 and −308 alleles and genotypes had no significant differences between the anti-HCV (+) and the anti-HCV (−) patients (p > 0.05). And the frequencies of the above alleles and genotypes were also approximately equally distributed in the persistent infection and in the viral clearance HD patients (p > 0.05). Conclusions: This study did not suggest that the TNF-α −238 and −308 polymorphisms had influence on the infection of HCV in Chinese HD patients.

show abstract

Discovery of Boceprevir and Narlaprevir: The First and Second Generation of HCV NS3 Protease Inhibitors

Chen

Njoroge

2012

Case Studies in Modern Drug Discovery and Development

View full text Add to dashboard Cite

Replicated Association Between an IL28B Gene Variant and a Sustained Response to Pegylated Interferon and Ribavirin

Cited by 299 publications

References 21 publications

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients

Tumor Necrosis Factor-α Promoter Gene Polymorphisms Are Not Associated with Hepatitis C Virus Infection in Chinese Hemodialysis Patients

Discovery of Boceprevir and Narlaprevir: The First and Second Generation of HCV NS3 Protease Inhibitors

Contact Info

Product

Resources

About