Ifnl4 and ifnl3 associated polymorphisms strongly influence the spontaneous ifnalpha receptor-1 expression in hcv-infected patients

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Abstract

Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4). The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFNbased therapy.

Original languageEnglish
Article numbere0117397
JournalPLoS One
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 12 2015

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interferons
Polymorphism
Interferons
Genes
Genotype
genetic polymorphism
Messenger RNA
receptors
genotype
therapeutics
loci
Proteins
genes
proteins
Linkage Disequilibrium
linkage disequilibrium
single nucleotide polymorphism
Single Nucleotide Polymorphism
Nucleotides
Therapeutics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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title = "Ifnl4 and ifnl3 associated polymorphisms strongly influence the spontaneous ifnalpha receptor-1 expression in hcv-infected patients",
abstract = "Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4). The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFNbased therapy.",
author = "Licia Bordi and Claudia Caglioti and Garbuglia, {Anna Rosa} and Daniele Lapa and Concetta Castilletti and Chiara Taibi and Capobianchi, {Maria Rosaria} and Eleonora Lalle",
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AU - Bordi, Licia

AU - Caglioti, Claudia

AU - Garbuglia, Anna Rosa

AU - Lapa, Daniele

AU - Castilletti, Concetta

AU - Taibi, Chiara

AU - Capobianchi, Maria Rosaria

AU - Lalle, Eleonora

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