title: IFNL4 and IFNL3 associated polymorphisms strongly influence the spontaneous IFN-alpha 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 IFN-based therapy.
authors: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.
authors: Licia
authors: L
authors: Bordi
authors: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.
authors: Claudia
authors: C
authors: Caglioti
authors: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.
authors: Anna Rosa
authors: AR
authors: Garbuglia
authors: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.
authors: Daniele
authors: D
authors: Lapa
authors: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.
authors: Concetta
authors: C
authors: Castilletti
authors: Clinical Department, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.
authors: Chiara
authors: C
authors: Taibi
authors: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.
authors: Maria Rosaria
authors: MR
authors: Capobianchi
authors: Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani," Rome, Italy.
authors: Eleonora
authors: E
authors: Lalle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D053633:Receptor, Interferon alpha-beta / Q000235:genetics*; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012333:RNA, Messenger; D053633:Receptor, Interferon alpha-beta; C507964:IFNAR1 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human