The Genetic Association of IFN-λs with Human Inflammatory Disorders Remains a Conundrum

Abstract

Type III Interferons (IFNs) or lambda IFNs (IFN-λs or IFNLs) although are primarily antiviral cytokines, may have roles to play in shaping immune responses, including those during inflammation. Genetic variants within the IFNL locus have been shown to be associated with various inflammatory conditions in humans ranging from metabolic to autoimmune and allergic diseases. The mechanism behind these genetic associations is not clear. Appropriate data analysis methods and functional evidence should be complimentarily used to identify the causal variants and mechanisms.

Keywords: IFN-λ3; IFN-λ4; IFNL locus; SNPs; inflammatory disorders.

Fig. 1

Three functional variants at the IFNL locus. IFN-λ3 functional variants can influence IFNL3 transcription (rs28416813; C allele increases and G allele decreases) or translation (rs4803217; G allele increases and T allele decreases) while IFN-λ4 functional variant gives rise to a new ORF for IFNL4 to be translated. The task of determining which of the 3 functional variants are likely causal to a given phenotype is challenging in the absence of alternate methods and unequivocal functional evidence. IFN-λ, interferon lambda; ORF open reading frame. Color images are available online.