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Title: IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.
Authors: Eslam, Mohammed
McLeod, Duncan
Kelaeng, Kebitsaone Simon
Mangia, Alessandra
Berg, Thomas
Thabet, Khaled
Irving, William L
Dore, Gregory J
Sheridan, David
Grønbæk, Henning
Abate, Maria Lorena
Hartmann, Rune
Bugianesi, Elisabetta
Spengler, Ulrich
Rojas, Angela
Booth, David R
Weltman, Martin
Mollison, Lindsay
Cheng, Wendy
Riordan, Stephen
Mahajan, Hema
Fischer, Janett
Nattermann, Jacob
Douglas, Mark W
Liddle, Christopher
Powell, Elizabeth
Romero-Gomez, Manuel
George, Jacob
International Liver Disease Genetics Consortium (ILDGC)
metadata.dc.subject.mesh: Fibrosis
Gene Frequency
Hepatitis C
Linkage Disequilibrium
Logistic Models
Multivariate Analysis
Polymorphism, Single Nucleotide
Reverse Transcriptase Polymerase Chain Reaction
Issue Date: 10-Apr-2017
Abstract: Genetic variation in the IFNL3-IFNL4 (interferon-λ3-interferon-λ4) region is associated with hepatic inflammation and fibrosis. Whether IFN-λ3 or IFN-λ4 protein drives this association is not known. We demonstrate that hepatic inflammation, fibrosis stage, fibrosis progression rate, hepatic infiltration of immune cells, IFN-λ3 expression, and serum sCD163 levels (a marker of activated macrophages) are greater in individuals with the IFNL3-IFNL4 risk haplotype that does not produce IFN-λ4, but produces IFN-λ3. No difference in these features was observed according to genotype at rs117648444, which encodes a substitution at position 70 of the IFN-λ4 protein and reduces IFN-λ4 activity, or between patients encoding functionally defective IFN-λ4 (IFN-λ4-Ser70) and those encoding fully active IFN-λ4-Pro70. The two proposed functional variants (rs368234815 and rs4803217) were not superior to the discovery SNP rs12979860 with respect to liver inflammation or fibrosis phenotype. IFN-λ3 rather than IFN-λ4 likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.
metadata.dc.identifier.doi: 10.1038/ng.3836
Appears in Collections:Producción 2020

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