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Two IL28B polymorphisms are associated with the treatment response of different genotypes of hepatitis C in different racial populations: A meta-analysis.

ABSTRACT: The purpose of this present meta-analysis is to provide an accurate estimation of the association between two IL28B polymorphisms (rs8099917 and rs12979860) and sustained virological response (SVR) to standard treatment of patients of different racial descent infected with different genotypes of hepatitis C virus (HCV), and also to investigate the possible factors in the IL28B gene that contribute to the different SVR rates of patients with different subtypes of HCV infection across different populations. The electronic database PubMed was searched. Asian patients with a common homozygote (TT vs. TG/GG, OR=3.17; CC vs. CT/TT, OR=3.75) attained a higher rate of SVR, and a similar result was observed in European patients (TT vs. TG/GG, OR=1.74; CC vs. CT/TT, OR=2.50). Furthermore, HCV1-infected patients with a common homozygote (TT vs. TG/GG, OR=2.95; CC vs. CT/TT, OR=4.34) appeared to have a higher SVR rate than those with HCV2/3 (TT vs. TG/GG, OR=1.56; CC vs. CT/TT, OR=1.37). The frequency of the common homozygote in Asian patients was high, followed by European patients and African patients. In all, Asian patients attained a higher SVR rate than European patients (P<0.05). Patients with HCV1 infection had a lower SVR rate than those with HCV2/3 infection (P<0.001). Our results suggest that both the common allele frequency and racial descent itself contribute to the difference in SVR rates across different population groups, and the common allele frequency may partly elucidate the different SVR rates in patients with different genotypes of HCV.

SUBMITTER: Wu LS

PROVIDER: S-EPMC3438700 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Two IL28B polymorphisms are associated with the treatment response of different genotypes of hepatitis C in different racial populations: A meta-analysis.

Wu Li-Sheng LS Wang Hong H Geng Xiao-Ping XP

Experimental and therapeutic medicine 20111121 2

The purpose of this present meta-analysis is to provide an accurate estimation of the association between two IL28B polymorphisms (rs8099917 and rs12979860) and sustained virological response (SVR) to standard treatment of patients of different racial descent infected with different genotypes of hepatitis C virus (HCV), and also to investigate the possible factors in the IL28B gene that contribute to the different SVR rates of patients with different subtypes of HCV infection across different po ...[more]

PMID: 22969869

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Project description:BackgroundHepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus (HCV) infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes.ObjectivesTo assess the associations of single nucleotide polymorphisms (SNP) of the IL28B and sustained virologic response (SVR) of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy.Materials and methodsWe searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate at SNP of the IL28B in individuals with PEG-interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied.ResultsThe sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans (OR = 3.85, 95% CI: 3.06-4.83); the percentage of rs12979860 TT genotype was lower in Caucasians (OR = 0.25, 95% CI: 0.20-0.31) and the percentage of rs12979860 CC genotype was higher in Caucasians than that of Afro-Americans (OR = 3.45, 95% CI = 2.68-4.44). Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 (OR = 0.16, 95% CI: 0.11-0.24).ConclusionsIL28B is significantly associated with response to PEG-interferon/ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes.

Project description:BackgroundMany studies have been published on the association between single nucleotide polymorphisms (SNP) near the IL28B gene and response to the combined treatments of pegylated-interferon (PegIFN) and ribavirin (RBV) in chronic HCV-infected patients, but without identical conclusions. The aim of this study was to assess impact of the IL28B polymorphisms on the effect of HCV standard treatment using meta-analysis based method.MethodsAssociation studies between polymorphisms of rs12979860 or rs8099917 and response to PegIFN/RBV treatment in chronic HCV patients were retrieved from PubMed. Data of qualified studies on sustained virological response (SVR) in different genotypes were extracted and analyzed using meta-analysis method in Stata 10 software.ResultsThirty-four papers, containing 46 independent studies, were included in the analysis. In the HCV G1/4 patients without treatment history, individuals carrying rs12979860 CC genotype were more likely to achieve SVR (OR 3.97, 95%CI 3.29-4.80) compared to those carrying CT/TT genotypes. Similar results were observed in the HCV G1/4 patients with unsuccessful or unknown treatment history (OR 3.76, 95%CI 2.67-5.28) or in the patients co-infected with human immunodeficiency virus (OR 5.20, 95%CI 3.04-8.90). However, associations could not be observed in HCV G2/3 patients. For rs8099917, similar results were obtained for genotype TT compared to genotypes TG/GG, indicating that TT genotype was significantly associated with better treatment response in patients infected with genotype 1 or 4 HCV, but not genotype 2 or 3 HCV.ConclusionPolymorphisms of rs12979860 and rs8099917 near IL28B only associate with the treatment response to PegIFN/RBV in patients infected with HCV genotype 1 or 4 but not with genotype 2 or 3, irrespective of the previous treatment history or HIV co-infected status. Therefore, identification of IL28B genotypes is necessary only in patients infected with relatively difficult-to-treat genotype 1 or 4 HCV.

Project description:BACKGROUND:IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon. OBJECTIVES:The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C. PATIENTS AND METHODS:In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS:The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46). CONCLUSIONS:It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.

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Two IL28B polymorphisms are associated with the treatment response of different genotypes of hepatitis C in different racial populations: A meta-analysis.

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Two IL28B polymorphisms are associated with the treatment response of different genotypes of hepatitis C in different racial populations: A meta-analysis.

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