Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C
| Autor: | Yolanda Real-Martínez, Carlos López-Larrea, Y. Rodríguez-Muñoz, Luis Rodrigo, M.J. Borque, Leticia González-Moreno, Paloma Sanz-Cameno, Luisa García-Buey, Javier Salmerón, Jose Ramón Vidal-Castiñeira, Paloma Rueda, Samuel Martín-Vílchez, Ricardo Moreno-Otero, Á. Hernández-Bartolomé, Rosario López-Rodríguez |
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| Přispěvatelé: | UAM. Departamento de Medicina, Instituto de Investigación del Hospital de La Princesa (IP) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
RNA viruses
Male 0301 basic medicine Heredity lcsh:Medicine Hepacivirus Pathology and Laboratory Medicine Biochemistry Polymorphism (computer science) Interferon Medicine and Health Sciences 2' 5'-Oligoadenylate Synthetase Medicine lcsh:Science Immune Response Chronic hepatitis Multidisciplinary Hepatitis C virus Liver Diseases Hepatitis C Medical microbiology Middle Aged Genetic Mapping Oncology Hepatocellular carcinoma Viruses Female Pathogens Research Article medicine.drug Adult medicine.medical_specialty Necroinflammatory activity Medicina Immunology Variant Genotypes Gastroenterology and Hepatology Carcinomas Microbiology Polymorphism Single Nucleotide 03 medical and health sciences Signs and Symptoms Suppressor of Cytokine Signaling 1 Protein Diagnostic Medicine Molecular genetics Gastrointestinal Tumors Endoribonucleases Genetics Humans Aspartate Aminotransferases Aged Inflammation TYK2 Kinase Flaviviruses business.industry Interleukins lcsh:R Organisms Viral pathogens Biology and Life Sciences Proteins Cancers and Neoplasms Human Genetics Hepatocellular Carcinoma Janus Kinase 1 Hepatitis C Chronic medicine.disease Fibrosis Hepatitis viruses Human genetics Patient’s genetic Microbial pathogens 030104 developmental biology Genetic marker lcsh:Q Interferons business Interferon pathways Developmental Biology |
| Zdroj: | PLoS ONE, Vol 12, Iss 7, p e0180927 (2017) Biblos-e Archivo. Repositorio Institucional de la UAM instname Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid PLoS ONE |
| Popis: | This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction 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. Methods 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. Results 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 (p < 0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels > 40 IU/L (p < 0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST ( > 40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p < 0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74). Conclusion 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 This work was supported by Ayudas Investigación Oncológica AIO-2010 to PSC ; Ayudas Proyectos de Investigación Fundación Mutua Madrileña 2010 to RMO; Ayudas Proyectos de Ayudas Proyectos de Investigación Fundación Mutua Madrileña 2012 to PSC; Programa Estatal de Investigación Fundamental Ministerio de Economía Industria y Competitividad SAF 2010-21805 to RMO |
| Databáze: | OpenAIRE |
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