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https://hdl.handle.net/2440/27479
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Type: | Journal article |
Title: | A novel I-TAC promoter polymorphic variant is functional in the presence of replicating HCV in vitro |
Author: | Helbig, K. George, J. Beard, M. |
Citation: | Journal of Clinical Virology, 2005; 32(2):137-143 |
Publisher: | Elsevier Science BV |
Issue Date: | 2005 |
ISSN: | 1386-6532 1873-5967 |
Abstract: | <h4>Background</h4>Chemokines are strong candidate genes for outcome of HCV infection. I-TAC is a chemokine known to be involved in the inflammatory process of HCV infection, and its expression is upregulated in chronic hepatitis C (CHC).<h4>Objectives</h4>The aim of this study was to investigate genetic variability in the I-TAC promoter and to determine the correlation of these variants with HCV disease progression.<h4>Study design</h4>I-TAC genotyping was performed in 60 chronic HCV patients and 60 controls using GeneScan analysis. Functional analysis of the I-TAC promoter was performed with the aid of luciferase reporter constructs transfected into Huh-7 cells or Huh-7 cells harbouring HCV genomic and sub-genomic replicons. Cytokine induced production of I-TAC from whole blood cultures was measured using enzyme-linked immunosorbent assay (ELISA).<h4>Results</h4>Sequencing of approximately 1 kb upstream of the I-TAC gene start codon revealed the presence of a novel 5 bp deletion mutant (-599del5) in a number of chronic HCV patients. Analysis of the functional potential of this deletion revealed no transcriptional change in Huh-7 cells transfected with luciferase reporter constructs, and this was confirmed in cytokine stimulated whole blood cultures where similar levels of I-TAC were liberated regardless of -599del5 genotype. Conversely, the -599del5 deletion variant significantly reduced transcriptional activity of the I-TAC promoter in the presence of replicating HCV. The distribution frequency of the allele was found to be significantly increased in a chronically HCV infected population compared to healthy controls.<h4>Conclusions</h4>The novel I-TAC -599del5 promoter polymorphism is a functional variant in the presence of replicating HCV. Furthermore, this deletion mutant is significantly increased in a chronic HCV cohort and may predispose to HCV disease susceptibility. |
Keywords: | HCV I-TAC Polymorphism Promoter |
Rights: | Copyright © 2004 Elsevier B.V. All rights reserved. |
DOI: | 10.1016/j.jcv.2004.10.001 |
Published version: | http://dx.doi.org/10.1016/j.jcv.2004.10.001 |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
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