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Review
, 7 (3), 231-42

The Role of Interferon-λ Locus Polymorphisms in Hepatitis C and Other Infectious Diseases

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Review

The Role of Interferon-λ Locus Polymorphisms in Hepatitis C and Other Infectious Diseases

Samantha J Griffiths et al. J Innate Immun.

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.

Figures

Fig. 1
Fig. 1
Location of SNPs in the IFN-λ gene locus. Schematic representation of the IFNL locus in chromosome 19q13, with key SNPs within non-coding and coding regions highlighted. SNPs discussed throughout this review are highlighted.
Fig. 2
Fig. 2
Regional LD plot with rs12979860. An LD plot was generated which highlights all SNPs within 50 bp up or downstream and in LD (r2 > 0.5) with rs12979860. SNPs discussed in this review, for which LD data is available, are highlighted. The plot was generated with SNP Annotation and Proxy Search (SNAP) using the 1000 Genomes Pilot 1 data set [101].
Fig. 3
Fig. 3
Geographical variations in rs12979860 allele frequency. Comparison of the relative frequency of C and T alleles in SNP rs12979860 in distinct worldwide regions (a) and in specific ethnic groups within Australia (b). Africa includes African Americans; Europe includes European Americans, and South America excludes the Ticuna population [adapted from [42, 98, 102]].

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