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A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure

Title: A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure
Authors: Corma-Gómez, Anaïs; Macías, Juan; Rivero, Antonio; Rivero-Juarez, Antonio; de Los Santos, Ignacio; Reus-Bañuls, Sergio; Morano, Luis; Merino, Dolores; Palacios, Rosario; Galera, Carlos; Fernández-Fuertes, Marta; González-Serna, Alejandro; de Rojas, Itziar; Ruiz, Agustín; Sáez, María E.; Real, Luis M.; Pineda, Juan A.
Contributors: Corma-Gómez,A; Macías,J; Fernández-Fuertes,M; González-Serna,A; Real,LM; Pineda,JA Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital de Valme, Sevilla, Spain. Macías,J; Pineda,JA Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain. Rivero,A; Rivero-Juarez,A Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Córdoba, Spain. de Los Santos,I Unidad de Medicina Interna y Enfermedades Infecciosas, Hospital de La Princesa, Madrid, Spain. Reus-Bañuls,S Unidad de Enfermedades Infecciosas, Hospital General Universitario de Alicante, Alicante, Spain. Morano,L Unidad de Patología Infecciosa, Hospital Universitario Alvaro Cunqueiro, Instituto de Investigación Sanitaria Galicia Sur (IISGS), Vigo, Spain. Merino,D Unidad de Enfermedades Infecciosas, Hospital Universitario Juan Ramón Jiménez, Huelva, Spain. Palacios,R Unidad de Enfermedades Infecciosas y Microbiología, Hospital Virgen de la Victoria, Málaga, Spain. Galera,C Unidad de Medicina Interna, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain. de Rojas,I; Ruiz,A Fundació ACE—Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya (UIC), Barcelona, Spain. de Rojas,I; Ruiz,A CIBERNED Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain. Sáez,ME Centro Andaluz de Estudios Bioinformáticos (CAEBI, SL), Sevilla, Spain. Real,LM Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Universidad de Málaga, Málaga, Spain.
Publisher Information: MDPI
Publication Year: 2021
Collection: Sistema Sanitario Público de Andalucía (SSPA): Repositorio
Subject Terms: GWAS; Hepatitis C virus infection; Polymorphisms; Sustained virological response; Direct-acting antivirals; Liver stiffness; Chromatin; DNA Packaging; Estudio de asociación del genoma completo; Hepatitis C; Hepacivirus; Polimorfismo de nucleótido simple; Antivirales; Cromatina; Empaquetamiento del ADN; Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans; Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents; Medical Subject Headings::Organisms::Viruses::Hepatitis Viruses::Hepacivirus; Medical Subject Headings::Diseases::Virus Diseases::Hepatitis; Viral; Human::Hepatitis C::Hepatitis C; Chronic; Medical Subject Headings::Analytical; Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies; Medical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genetic Research::Gene Ontology; Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism; Genetic::Polymorphism; Single Nucleotide; Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cell Nucleus::Cell Nucleus Structures::Intranuclear Space::Chromosomes::Chromosome Structures::Chromatin; Medical Subject Headings::Phenomena and Processes::Biological Phenomena
Description: Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes. ; This work was supported by a grant from the Consejería de Salud de la Junta de An dalucía (project PI-0001/2017), and partially founded by the Instituto de Salud Carlos III (Projects PI16/01443 and PI19/01312), integrated in the national I+D+i 2013–2016, 2016–2019, and co-funded by the European Union (ERDF/ESF, “Investing in your future”), by the Spanish Network for AIDS investigation (RIS) (www.red.es/redes/inicio (accessed on 1 January 2021)) (RD16/0025/0040), as a part of the Nacional I+ D+I, ISCIII Subdirección General de Evaluación and the European Fund for Development of Regions (FEDER) and ...
Document Type: article in journal/newspaper
File Description: 11 p.; application/pdf; application/vnd.openxmlformats-officedocument.presentationml.presentation
Language: English
ISSN: 2075-4418
Relation: https://www.mdpi.com/2075-4418/11/8/1501/htm; Corma-Gómez A, Macías J, Rivero A, Rivero-Juarez A, de Los Santos I, Reus-Bañuls S, et al. A Genome-Wide Association Study on Liver Stiffness Changes during Hepatitis C Virus Infection Cure. Diagnostics. 2021 Aug 20;11(8):1501; http://hdl.handle.net/10668/4346; PMC8394459
DOI: 10.3390/diagnostics11081501
Availability: http://hdl.handle.net/10668/4346; https://doi.org/10.3390/diagnostics11081501
Rights: Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0/ ; open access
Accession Number: edsbas.D454F9F8
Database: BASE