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Title: Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.
Authors: López-Rodríguez, Rosario
Hernández-Bartolomé, Ángel
Borque, María Jesús
Rodríguez-Muñoz, Yolanda
Martín-Vílchez, Samuel
García-Buey, Luisa
González-Moreno, Leticia
Real-Martínez, Yolanda
Muñoz de Rueda, Paloma
Salmerón, Javier
Vidal-Castiñeira, José Ramón
López-Larrea, Carlos
Rodrigo, Luis
Moreno-Otero, Ricardo
Sanz-Cameno, Paloma
metadata.dc.subject.mesh: 2',5'-Oligoadenylate Synthetase
Aspartate Aminotransferases
Hepatitis C, Chronic
Janus Kinase 1
Middle Aged
Polymorphism, Single Nucleotide
Suppressor of Cytokine Signaling 1 Protein
TYK2 Kinase
Issue Date: 12-Jul-2017
Abstract: Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p40 IU/L (p40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.
metadata.dc.identifier.doi: 10.1371/journal.pone.0180927
Appears in Collections:Producción 2020

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