IFNL4: Notable variants and associated phenotypes.
Gene
; 730: 144289, 2020 Mar 10.
Article
em En
| MEDLINE
| ID: mdl-31846709
ABSTRACT
Interferon lambda proteins activate the JAK-STAT signalling pathway, resulting in upregulation of genes with antiviral effects. The interferon lambda family was initially thought to be redundant to the interferon alpha family, which signals through the same pathway, except for the more limited expression of the IFNLR1 receptor. However, recent studies show that interferon lambdas uniquely protect tissue barriers against a wide range of important viral infections. The interferon lambda 4 gene (IFNL4) was discovered in 2013. The IFNL4 protein is determined by the IFNL4-ΔG/TT (rs368234815) variant. The ancestral IFNL4-ΔG allele generates IFNL4, whereas IFNL4-TT causes pre-mature termination of the protein. Surprisingly, although interferons are generally antiviral proteins, the genotypes that generate the IFNL4 protein are strongly linked to impaired clearance of hepatitis C virus (HCV). IFNL4 genotype has also been linked to variation within the HCV genome, as well as risk of hepatic fibrosis, certain cancers and some infectious diseases. There has been very strong evolutionary selection against the ancestral IFNL4-ΔG allele, which is the major form in African populations, but the minor allele in Europeans and Asians. The reason for this selection and the biological mechanisms underlying observed phenotypic associations remain to be explained.
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Base de dados:
MEDLINE
Assunto principal:
Interleucinas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article