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Interleukin 28B-related polymorphisms: a pathway for understanding hepatitis C virus infection?

ABSTRACT: AIM:To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians. METHODS:A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon ?-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients. RESULTS:SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07). CONCLUSION:The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.

SUBMITTER: Garcia RF

PROVIDER: S-EPMC3831221 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Interleukin 28B-related polymorphisms: a pathway for understanding hepatitis C virus infection?

Garcia Raquel Francine Liermann RF Moreira Simone S de Araújo Ramos Ana Lucia AL Ferreira Leslie Ecker LE de Mattos Angelo Alves AA Tovo Cristiane Valle CV Nader Lysandro Alsina LA Ramos Juliene Antonio JA Rondinelli Edson E de Jesus Dominici Arnaldo A Garcia Christian Evangelista CE de Souza Leite Pinho Mauro M Brandão-Mello Carlos Eduardo CE Villela-Nogueira Cristiane Alves CA de França Paulo Henrique Condeixa PH

World journal of gastroenterology 20131101 42

<h4>Aim</h4>To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.<h4>Methods</h4>A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on ...[more]

PMID: 24259970

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Project description:BackgroundThis meta-analysis aimed to assess available evidence on possible associations of interleukin-28B polymorphisms rs8099917 and rs12979860 with development of hepatitis virus-related hepatocellular carcinoma (HCC).MethodsPubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Meta-analyses were performed to examine the association of interleukin-28B rs8099917 G/T and rs12979860 T/C polymorphisms with development of hepatitis virus-related HCC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsA total of ten studies involving 2,529 cases and 2,412 controls were included. The G-allele and GT genotype of rs8099917 were significantly associated with increased risk of hepatitis B virus (HBV)-related HCC (allelic model, OR 1.49, 95% CI 1.13-1.96, P=0.005; heterozygous model, OR 1.39, 95% CI 1.04-1.88, P=0.03). Conversely, the TT genotype was found to be significantly associated with lower risk of HBV-related HCC (dominant model, OR 0.68, 95% CI 0.51-0.91, P=0.01). Similar results were observed in the subgroup of Chinese patients and controls. In the pooled data set, the T-allele and TT genotype of rs12979860 showed a significant association with increased HCC risk (allelic model, OR 1.36, 95% CI 1.05-1.78, P=0.02; recessive model, OR 1.75, 95% CI 1.28-2.39, P=0.005; homozygous model, OR 1.99, 95% CI 1.41-2.80, P<0.001). Subgroup analysis based on ethnicity and etiology showed rs12979860 polymorphism to be significantly associated with HCC risk in Caucasians, especially hepatitis C virus-related HCC, according to all five genetic models. In contrast, only the TT genotype of rs12979860 was found to be significantly associated with increased risk of HBV-related HCC, especially in Asians.ConclusionThe G-allele of rs8099917 may confer elevated risk of HBV-related HCC, while the wild-type TT genotype may protect against the disease. The T-allele of rs12979860 may increase the risk of HCC, in Caucasians, especially hepatitis C virus-related HCC. The TT genotype of rs12979860 may confer increased risk of HBV-related HCC, especially in Asians. These conclusions should be verified in large, well-designed studies.

Project description:UNLABELLED:Polymorphisms in the IL28B (interleukin-28B) gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C (ATAHC) was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n = 52) or had persistent infection (infection duration ?26 weeks) at treatment initiation (n = 80). Spontaneous clearance was observed in 23% (30 of 132 participants). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (adjusted hazards ratio = 2.86; 95% confidence interval = 1.24, 6.59; P = 0.014). Among participants with IL28B genotyping (n = 102 of 163 overall and 79 of 132 for the spontaneous clearance population), rs8099917 TT homozygosity (versus GT/GG) was the only factor independently predicting time to spontaneous clearance (adjusted hazard ratio = 3.78; 95% confidence interval = 1.04, 13.76; P = 0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P = 0.047). Among participants adherent to treatment and who had IL28B genotyping (n = 54), sustained virologic response was similar among TT homozygotes (18 of 29 participants, 62%) and those with GG/GT genotype (16 of 25, 64%, P = 0.884). CONCLUSION:During recent HCV infection, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes.

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Interleukin 28B-related polymorphisms: a pathway for understanding hepatitis C virus infection?

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Interleukin 28B-related polymorphisms: a pathway for understanding hepatitis C virus infection?

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