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The IFN-? Genetic Polymorphism Association With the Viral Clearance Induced by Hepatitis C Virus Treatment in Pakistani Patients.

ABSTRACT: BACKGROUND:Polymorphisms in the interferon ? (INF ?) genes on chromosome 19 have been associated with clearance of hepatitis C virus (HCV) induced by interferon and ribavirin therapy however there is no such data available for Pakistani patients with HCV infection. OBJECTIVES:In this study, the effects of single nucleotide polymorphisms (SNPs) have been investigated in response to treatment with interferon-? and ribavirin in a cohort of 75 HCV genotype 3a patients. PATIENTS AND METHODS:A total number of 50 SNPs from the Interferon ? region on chromosome 19 were genotyped to investigate allelic associations with the treatment response in HCV type 3a patients. Thirteen SNPs were associated with HCV clearance, with the most significant alleles being RS8109886 (Fisher's P = 0.0001), RS8113007 (Fisher's P = 0.0001) and RS12979860 (Fisher's P = 0.0002). RESULTS:These SNPs were found to be the most suitable SNPs for predicting treatment response in the present study. These findings support those reported previously. This could be used to improve HCV treatment strategies and suggest that Pakistani patients should be genotyped for the relevant SNPs to identify the patients who are more likely to respond to interferon and ribavirin therapy. CONCLUSIONS:This therapy is costly and can be accompanied by several adverse side-effects, hence pre-treatment prediction of patients who are most likely to benefit would have both economic and patient benefits in the long term.

SUBMITTER: Tipu I

PROVIDER: S-EPMC3984471 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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The IFN-λ Genetic Polymorphism Association With the Viral Clearance Induced by Hepatitis C Virus Treatment in Pakistani Patients.

Tipu Imran I Marriage Fiona F Farooqi Zia-Ur-Rahman ZU Platt Hazel H Athar Muhammad Amin MA Day Philip John PJ Short Andrea A

Hepatitis monthly 20140309 3

<h4>Background</h4>Polymorphisms in the interferon λ (INF λ) genes on chromosome 19 have been associated with clearance of hepatitis C virus (HCV) induced by interferon and ribavirin therapy however there is no such data available for Pakistani patients with HCV infection.<h4>Objectives</h4>In this study, the effects of single nucleotide polymorphisms (SNPs) have been investigated in response to treatment with interferon-α and ribavirin in a cohort of 75 HCV genotype 3a patients.<h4>Patients and ...[more]

PMID: 24734091

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Project description:BackgroundIn non-uremic subjects, IFNL4 rs368234815 predicts HCV clearance. We investigated whether rs368234815 is associated with spontaneous HCV clearance in haemodialysis patients and whether it is a stronger predictor of HCV resolution than the IFNL polymorphisms already associated with HCV clearance in dialysis subjects. We also evaluated an association of rs368234815 with patients` survival and alterations in transcription factor binding sites (TFBS) caused by IFNL polymorphisms.MethodsAmong 161 haemodialysis patients with positive anti-HCV antibodies, 68 (42.2%) spontaneously resolved HCV infection, whereas 93 remained HCV RNA positive. Patients were tested for near IFNL3 rs12980275, IFNL3 rs4803217, IFNL4 rs12979860, IFNL4 rs368234815, and near IFNL4 rs8099917. IFNL4 rs368234815 polymorphism (TT/TT, ΔG/TT, ΔG/ΔG) was genotyped by restriction fragment length polymorphism analysis; other IFNL polymorphisms - by high resolution melting curve analysis. We used the Kaplan-Meier method with the log-rank test for survival analysis. In silico analysis included the use of ENCODE TFBS ChIP-seq data, HOCOMOCO, JASPAR CORE, and CIS-BP databases, and FIMO software.ResultsThe probability (OR, 95%CI, P) of spontaneous HCV clearance for rs368234815 TT/TT patients was higher than for the ΔG allele carriers (2.63, 1.38-5.04, 0.003). This probability for other major homozygotes varied between 2.80, 1.45-5.43, 0.002 for rs12980275 and 2.44, 1.27-4.69, 0.007 for rs12979860. In the additive model, rs368234815 TT/TT was the strongest predictor of HCV clearance (6.38, 1.69-24.2, 0.003). Survival analysis suggested an association of the ΔG allele with mortality due to neoplasms (log-rank P = 0.005). The rs368234815 ∆G allele caused TFBS removal for PLAGL1.ConclusionsIn haemodialysis patients, the association of rs368234815 with the spontaneous HCV clearance is better than that documented for other IFNL3/IFNL4 polymorphisms only in the additive mode of inheritance. However, identifying the homozygosity in the variant ∆G allele of rs368234815 means a more potent prediction of persistent HCV infection in haemodialysis subjects that we observe in the case of the variant homozygosity of other tested IFNL3/IFNL4 polymorphisms. Removal of PLAGL1 TFBS in subjects harbouring the rs368234815 ∆G allele may contribute to cancer susceptibility. The association of rs368234815 with cancer-related mortality needs further studies in HCV-exposed subjects.

Dataset Information

The IFN-? Genetic Polymorphism Association With the Viral Clearance Induced by Hepatitis C Virus Treatment in Pakistani Patients.

Publications

The IFN-λ Genetic Polymorphism Association With the Viral Clearance Induced by Hepatitis C Virus Treatment in Pakistani Patients.

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