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http://purl.uniprot.org/citations/15653416http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15653416http://www.w3.org/2000/01/rdf-schema#comment"

Background

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).

Objectives

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.

Study design

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).

Results

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.

Conclusions

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."xsd:string
http://purl.uniprot.org/citations/15653416http://purl.org/dc/terms/identifier"doi:10.1016/j.jcv.2004.10.001"xsd:string
http://purl.uniprot.org/citations/15653416http://purl.uniprot.org/core/author"George J."xsd:string
http://purl.uniprot.org/citations/15653416http://purl.uniprot.org/core/author"Beard M.R."xsd:string
http://purl.uniprot.org/citations/15653416http://purl.uniprot.org/core/author"Helbig K.J."xsd:string
http://purl.uniprot.org/citations/15653416http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15653416http://purl.uniprot.org/core/name"J Clin Virol"xsd:string
http://purl.uniprot.org/citations/15653416http://purl.uniprot.org/core/pages"137-143"xsd:string
http://purl.uniprot.org/citations/15653416http://purl.uniprot.org/core/title"A novel I-TAC promoter polymorphic variant is functional in the presence of replicating HCV in vitro."xsd:string
http://purl.uniprot.org/citations/15653416http://purl.uniprot.org/core/volume"32"xsd:string
http://purl.uniprot.org/citations/15653416http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15653416
http://purl.uniprot.org/citations/15653416http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15653416
http://purl.uniprot.org/uniprot/#_O14625-mappedCitation-15653416http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15653416
http://purl.uniprot.org/uniprot/#_Q96KF0-mappedCitation-15653416http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15653416
http://purl.uniprot.org/uniprot/Q96KF0http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15653416
http://purl.uniprot.org/uniprot/O14625http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15653416