Actividad Investigadora
Identification of a 3'-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study
Fecha de publicación:
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Autores de IDIVAL
Autores ajenos al IDIVAL
- Carmona FD
- Vicente, Esther F.
- Pulito-Cueto, Veronica
- Ramirez Huaranga, Marco A.
- Robustillo-Villarino, Montserrat
- Rodriguez-Carrio, Javier
- Alperi-Lopez, Mercedes
- Alegre-Sancho, Juan J.
- Lera-Gomez, Leticia
- Perez-Pampin, Eva
- Ortega-Castro, Rafaela
- Lopez-Pedrera, Chary
- Garcia Vivar, Mari L.
- Gomez-Arango, Catalina
- Raya, Enrique
- Narvaez, Javier
- Balsa, Alejandro
- Lopez-Longo, Francisco J.
- Carreira, Patricia
- Gonzalez-Alvaro, Isidoro
- Rodriguez-Rodriguez, Luis
- Fernandez-Gutierrez, Benjamin
- Ferraz-Amaro, Ivan
- Gualillo, Oreste
- Castañeda S
- Martin, Javier
Unidades
Abstract
Objective To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). Methods We performed a genome-wide association study (GWAS) in which, after quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analyzed in 2,989 RA patients of European origin. Data on subclinical atherosclerosis, obtained through assessment of carotid intima-media thickness (CIMT) and presence/absence of carotid plaques by carotid ultrasonography, were available for 1,355 individuals. Results A genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome-wide level of significance (minor allele [G] beta coefficient 0.142, P = 1.86 x 10(-8)). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biologic pathway enrichment and predictive protein-protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (Gene Ontology no. 0032964; false discovery rate-adjusted P = 4.01 x 10(-3)). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB1, MSRA, and ZC3HC1 (P = 8.12 x 10(-4), P = 5.94 x 10(-4), and P = 2.46 x 10(-4), respectively). Conclusion The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA.
© 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
Datos de la publicación
- ISSN/ISSNe:
- 2326-5191, 2326-5205
- Tipo:
- Article
- Páginas:
- 351-360
- DOI:
- 10.1002/art.40734
- PubMed:
- 30251476
Arthritis & Rheumatology WILEY-BLACKWELL
Citas Recibidas en Web of Science: 25
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