title: The Role of Interferon-λ Locus Polymorphisms in Hepatitis C and Other Infectious Diseases.
abstract: Since its discovery in 2003, the type III interferon-λ (IFN-λ) family has been found to contribute significantly to the host response to infection. Whilst IFN-λ shares many features with type I IFN induction and signalling pathways, the tissue-specific restricted expression of its receptor, IL28RA, makes IFN-λ a major mediator of host innate immunity in tissues and organs with a high epithelial cell content. Host susceptibility and responses to infection are known to be heterogeneous, and the identification of common genetic variants linked to disease outcome by genome-wide association studies (GWAS) has underscored the significance of host polymorphisms in responses to infection. Several such GWAS have highlighted the IFN-λ locus on chromosome 19q13 as an area of genetic variation significantly associated with hepatitis C virus (HCV) infection, and the rs12979860 genotype can be used in clinical practice as a biomarker for predicting a successful response to treatment with pegylated IFN and ribavarin. Here, we discuss IFN-λ genetic polymorphisms and their role in HCV and other infectious diseases as well as their potential impact on clinical diagnostics, patient stratification and therapy. Finally, the broader role of IFN-λ in the immunopathogenesis of non-infectious inflammatory diseases is considered.
authors: Division of Infection and Pathway Medicine, University of Edinburgh Medical School, Edinburgh, UK.
authors: Samantha J
authors: SJ
authors: Griffiths
authors: Cory M
authors: CM
authors: Dunnigan
authors: Clark D
authors: CD
authors: Russell
authors: Jürgen G
authors: JG
authors: Haas
mesh_terms: D000818:Animals; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics / Q000276:immunology; D056426:Genetic Loci / Q000276:immunology*; D055106:Genome-Wide Association Study; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic / Q000276:immunology*; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D017471:Receptors, Interferon
chemical_list: C579640:IFNLR1 protein, human; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D007372:Interferons
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