Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2017; 23(21): 3815-3824
Published online Jun 7, 2017. doi: 10.3748/wjg.v23.i21.3815
Prevalence of IFNL3 rs4803217 single nucleotide polymorphism and clinical course of chronic hepatitis C
Bogna Świątek-Kościelna, Ewelina Kałużna, Ewa Strauss, Jerzy Nowak, Iwona Bereszyńska, Ewelina Gowin, Danuta Januszkiewicz-Lewandowska, Iwona Mozer-Lisewska, Dominika Barcińska, Jolanta Rembowska, Jacek Wysocki
Bogna Świątek-Kościelna, Ewelina Kałużna, Ewa Strauss, Jerzy Nowak, Jolanta Rembowska, Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland, 60-479 Poznan, Poland
Ewa Strauss, Department of General and Vascular Surgery, Poznan University of Medical Sciences, 61-848 Poznan, Poland
Iwona Bereszyńska, Iwona Mozer-Lisewska, Department of Infectious Diseases, Poznan University of Medical Sciences, 61-288 Poznan, Poland
Ewelina Gowin, Department of Family Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland
Jacek Wysocki, Department of Preventive Medicine, Poznan University of Medical Sciences, 60-179 Poznan, Poland
Dominika Barcińska, Department of Medical Diagnostics, 60-595 Poznan, Poland
Danuta Januszkiewicz-Lewandowska, Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, 60-572 Poznan, Poland
Danuta Januszkiewicz-Lewandowska, Department of Medical Diagnostics, 60-595 Poznan, Poland
Author contributions: Świątek-Kościelna B, Kałużna E and Strauss E contributed equally to this work; Świątek-Kościelna B, Kałużna E, Nowak J, Bereszyńska I, Gowin E, Wysocki J, Mozer-Lisewska I and Januszkiewicz-Lewandowska D substantially contributed to the conception and design of the study, samples and data collection and interpretation of results; Świątek-Kościelna B, Kałużna E, Rembowska J and Barcińska D performed the experiments; Świątek-Kościelna B and Strauss E analyzed the results; all authors drafted the article and made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published; Świątek-Kościelna B, Kałużna E and Strauss E contributed equally to this work.
Institutional review board statement: The study was approved by the Bioethics Committee of the Poznan University of Medical Sciences (No. 650/12).
Conflict-of-interest statement: All authors declare no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Danuta Januszkiewicz-Lewandowska, MD, PhD, Professor, Department of Pediatric Oncology, Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland. danuta.januszkiewicz@ump.edu.pl
Telephone: +48-60-1781821 Fax: +48-61-8233235
Received: January 27, 2017
Peer-review started: February 12, 2017
First decision: March 3, 2017
Revised: March 17, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: June 7, 2017
Processing time: 130 Days and 9.2 Hours
Abstract
AIM

To evaluate the association of IFNL3 (IL28B) SNP rs4803217 with severity of disease and treatment outcome in chronic hepatitis C (CHC).

METHODS

The study enrolled 196 CHC Polish patients (82 women and 114 men in age 20-64) infected with hepatitis C virus (HCV) genotype 1. They were treatment naïve and qualified to pegylated interferon alpha (PEG-IFN-α) and ribavirin (RBV) therapy. The analyzed baseline parameters included: degree of inflammation, stage of fibrosis, viral load as well as alanine aminotransferase (ALT), asparagine aminotransferase (AST) and total bilirubin (TBIL). The analysis of response to therapy included: sustained virological response (SVR), defined as undetectable serum HCV RNA level six month after completion of 48-wk therapy, and relapse, defined as achieving undetectable viral load at the end of treatment but not SVR. HCV genotyping and HCV RNA quantification were performed using commercially available tests. DNA was isolated from peripheral blood mononuclear cells or from buccal cell swabs. In addition to rs4803217, also single nucleotide polymorphisms (SNPs) (rs12979860, rs8099917 and rs12980275) of known significance in predicting of HCV clearance were analyzed. SNPs were determined by high resolution melt analysis and confirmed by sequencing of amplicons.

RESULTS

Frequency of rs4803217 genotypes in studied group was as follows: 27.55%; 54.59% and 17.86% for CC, CA and AA, respectively. The rs4803217 SNP, similar to other analyzed SNPs, was not associated with severity of CHC (grade of inflammation, stage of fibrosis, baseline viral load as well as biochemical parameters: ALT, AST, TBIL). It was demonstrated that the rs4803217C allele is associated with SVR (C vs A: P < 0.0001; dose of C allele: P = 0.0002) and non-relapse (C vs A: P = 0.001; dose of C allele: P = 0.002). Moreover, it was found that patients with CC genotype have significantly higher response rates as compared with CA/AA patients (P < 0.0001), whereas patients carrying A allele are significantly predisposed to relapse after treatment (P = 0.0007). Moreover, the association of rs4803217 with SVR was comparable to that of rs12979860 and stronger as observed for rs12980275 and rs8099917. Association of rs4803217 with relapse, was the strongest as compared with the other SNPs. The analysis of combined rs4803217 and rs8099917 genotypes demonstrated that additional genotyping of rs8099917 had no significant impact on the prediction of SVR. Multivariate analysis revealed that among analyzed SNPs only rs4803217 is an independent predictor of SVR (P = 0.016) and relapse (P = 0.024).

CONCLUSION

The rs4803217 SNP is a strong, independent and superior predictor of SVR and relapse in HCV genotype 1 infected CHC patients treated with PEG-IFN-α and RBV.

Keywords: Hepatitis C virus; Chronic hepatitis C; Interferon lambda 3; Interleukin 28B; rs4803217

Core tip: The rs4803217 single nucleotide polymorphism of IFNL3 (IL28B) gene, which encodes, interferon lambda 3 (interleukin 28B), has been proposed as a causal variant that may influence hepatitis C virus (HCV) clearance. In the present study it was found that rs4803217 is a strong and independent predictor of sustained virological response and relapse in HCV genotype 1 infected chronic hepatitis C patients treated with pegylated interferon alpha and ribavirin. Moreover, it was indicated that rs4803217 seems to be much better predictor of therapy outcome than well-establish IFNL3 SNPs (rs12979860, rs8099917 and rs12980275).