Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/17885
Título
A Combined Transcriptomic and Genomic Analysis Identifies a Gene Signature Associated With the Response to Anti-TNF Therapy in Rheumatoid Arthritis
Autor(es)
Aterido, Adrià | Cañete, Juan D | Tornero, Jesús | Blanco, Francisco | Fernández-Gutierrez, Benjamín | Pérez, Carolina | Alperi-López, Mercedes | Olivè, Alex | Corominas, Héctor | Martínez-Taboada, Víctor | González, Isidoro | Fernández-Nebro, Antonio | Erra, Alba | López-Lasanta, María | López Corbeto, Mireia | Palau, Núria | Marsal, Sara | Julià, Antonio
Fecha de publicación
2019-07-02
Idioma
Inglés
Tipo de documento
research article
Resumen
Background: Rheumatoid arthritis (RA) is the most frequent autoimmune disease involving the joints. Although anti-TNF therapies have proven effective in the management of RA, approximately one third of patients do not show a significant clinical response. The objective of this study was to identify new genetic variation associated with the clinical response to anti-TNF therapy in RA. Methods: We performed a sequential multi-omic analysis integrating different sources of molecular information. First, we extracted the RNA from synovial biopsies of 11 RA patients starting anti-TNF therapy to identify gene coexpression modules (GCMs) in the RA synovium. Second, we analyzed the transcriptomic association between each GCM and the clinical response to anti-TNF therapy. The clinical response was determined at week 14 using the EULAR criteria. Third, we analyzed the association between the GCMs and anti-TNF response at the genetic level. For this objective, we used genome-wide data from a cohort of 348 anti-TNF treated patients from Spain. The GCMs that were significantly associated with the anti-TNF response were then tested for validation in an independent cohort of 2,706 anti-TNF treated patients. Finally, the functional implication of the validated GCMs was evaluated via pathway and cell type epigenetic enrichment analyses. Results: A total of 149 GCMs were identified in the RA synovium. From these, 13 GCMs were found to be significantly associated with anti-TNF response (P
Palabras clave
anti-TNF therapy | Genomics | Multi-omics association analysis | Rheumatoid arthritis | Transcriptomics
MESH
Adalimumab | Antirheumatic Agents | Arthritis, Rheumatoid | Biopsy | Cohort Studies | Female | Gene Regulatory Networks | Genome-Wide Association Study | Humans | Infliximab | Male | Polymorphism, Single Nucleotide | Synovial Membrane | Transcriptome | Treatment Outcome | Tumor Necrosis Factor-alpha
DOI
Aparece en las colecciones
- Investigación > IIS > IDIBAPS - Instituto de Investigaciones Biomédicas August Pi i Sunyer (Cataluña)
- Investigación > IIS > IBIMA-Plataforma BIONAND - Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina (Andalucía)
- Investigación > IIS > IIS-PRINCESA - Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (Madrid)
- Investigación > IIS > INIBIC - Instituto de Investigación Biomédica A Coruña (Galicia)
- Investigación > IIS > IR-HUVH - Instituto de Investigación Hospital Universitari Vall d’Hebron (Cataluña)
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