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This work was supported by a grant from the Consejeria de Salud de la Junta de Andalucia (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 Subdireccion General de Evaluacion and the European Fund for Development of Regions (FEDER) and by GEHEP-SEIMC (GEHEP-011 project). J.A.P. has received a research extension grant from the Programa de Intensificacion de la Actividad de Investigacion del Servicio Nacional de Salud Carlos III (I3SNS). A.C.-G. has received a Rio Hortega grant from the Instituto de Salud Carlos III (grant number CM19/00251). A.G.-S. is the recipient of a Miguel Servet Research Contract by Instituto de Salud Carlos III (CP18/00146). I.R. is the recipient of a P-FIS Research Contract by Instituto de Salud Carlos IIII (FI20/00215). A.Ruiz. is supported by national grants PI13/02434, PI16/01861 and PI19/01301. Accion Estrategica en Salud is integrated into the Spanish National R+ D+ I Plan and funded by ISCIII (Instituto de Salud Carlos III), Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER "Una manera de Hacer Europa") and received support from the European Union/EFPIA Innovative Medicines Initiative Joint Undertaking ADAPTED and MOPEAD projects (Grants No. 115975 and 115985) and PREADAPT project (JPco-fuND-2. Grant number AC19/00097).

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

Publicado en:Diagnostics. 11 (8): 1501- - 2021-08-01 11(8), DOI: 10.3390/diagnostics11081501

Autores: Corma-Gomez, Anais; Macias, Juan; Rivero, Antonio; Rivero-Juarez, Antonio; de los Santos, Ignacio; Reus-Banuls, Sergio; Morano, Luis; Merino, Dolores; Palacios, Rosario; Galera, Carlos; Fernandez-Fuertes, Marta; Gonzalez-Serna, Alejandro; de Rojas, Itziar; Ruiz, Agustin; Saez, Maria E.; Real, Luis M.; Pineda, Juan A.;

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Resumen

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.

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