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IL28B rs12979860 genotype and spontaneous clearance of hepatitis C virus in a multi-ethnic cohort of injection drug users: evidence for a supra-additive association.

ABSTRACT: Among 1369 Urban Health Study participants, we evaluated genetic models for the association of IL28B genotype (rs12979860 and rs8099917) with hepatitis C virus (HCV) clearance. For rs12979860, adjusted odds ratios for spontaneous HCV clearance were as follows: IL28B-CC, 3.88 (P < .001); IL28B-CT, 1.48 (P = .08). On the basis of Akaike information criteria values and ?(2) tests, a supra-additive (quadratic) model fit these data best. Models based on rs8099917 provided poorer fit. Evidence that a supra-additive rs12979860-based model best fits the association of IL28B-genotype with HCV clearance may improve clinical prediction models and foster a better understanding of functional mechanisms underlying this association.

SUBMITTER: Shebl FM

PROVIDER: S-EPMC3209810 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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IL28B rs12979860 genotype and spontaneous clearance of hepatitis C virus in a multi-ethnic cohort of injection drug users: evidence for a supra-additive association.

Shebl Fatma M FM Pfeiffer Ruth M RM Buckett Dianna D Muchmore Brian B Chen Sabrina S Dotrang Myhanh M Prokunina-Olsson Ludmila L Edlin Brian R BR O'Brien Thomas R TR

The Journal of infectious diseases 20111019 12

Among 1369 Urban Health Study participants, we evaluated genetic models for the association of IL28B genotype (rs12979860 and rs8099917) with hepatitis C virus (HCV) clearance. For rs12979860, adjusted odds ratios for spontaneous HCV clearance were as follows: IL28B-CC, 3.88 (P < .001); IL28B-CT, 1.48 (P = .08). On the basis of Akaike information criteria values and χ(2) tests, a supra-additive (quadratic) model fit these data best. Models based on rs8099917 provided poorer fit. Evidence that a ...[more]

PMID: 22013224

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Project description:Background and aimsGenetic polymorphisms near interleukin 28B gene are associated with spontaneous and treatment induced clearance of hepatitis C virus (HCV). Our objective was to evaluate the impact of interleukin 28B single nucleotide polymorphism (rs12979860, rs8099917) variability in HCV genotype 3 infected populations.Methods400 hepatitis C seroreactive patients from different population groups in Eastern and North Eastern part of India were assessed for host and viral genotypic analysis. 83 HCV genotype 3 infected patients were administered pegylated interferon- ribavirin therapy. Viral genotyping was performed using nested reverse transcriptase-PCR followed by direct sequencing methods. Host interleukin 28B genotyping was performed using real-time PCR based single nucleotide polymorphism analysis.ResultsOut of 400 hepatitis C seroreactive individuals, 73.25% were found to be RNA positive. HCV genotype 3 (65.87%) was found to be the major circulating strain in this region followed by genotype 1 (32.08%). rs12979860 CC genotype was significantly associated with sustained virological response in HCV genotype 3 infected population. In patients achieving rapid virological response, favourable CC/TT allele at rs12979860, rs8099917 was found to be predominant at both the alleles at 77%, 73.2% respectively; whereas in case of patients with relapsed HCV infection CT, TG alleles were found to be predominant. Additionally, CC genotypes at rs12979860 were found to be associated with sustained virological response in patients with high viral load (OR = 6.75, 0.05<p). HCV unfavourable rs12979860 TT, rs8099917 GG alleles were present in 34%, 27.6% patients with relapsed HCV infection respectively. Also unfavourable CT, TG genotypes were found to be predominant in patients with advanced stages of liver disease.ConclusionCC, TT the two favourable markers at SNPs rs12979860 and rs8099917 are strongly associated with sustained virological response in genotype 3 infected populations. This information will aid clinicians to effectively design response based treatment regimen.

Dataset Information

IL28B rs12979860 genotype and spontaneous clearance of hepatitis C virus in a multi-ethnic cohort of injection drug users: evidence for a supra-additive association.

Publications

IL28B rs12979860 genotype and spontaneous clearance of hepatitis C virus in a multi-ethnic cohort of injection drug users: evidence for a supra-additive association.

Similar Datasets

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