RT Journal Article
T1 Identification of a 3'-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study.
A1 López-Mejías, Raquel
A1 Carmona, F David
A1 Genre, Fernanda
A1 Remuzgo-Martínez, Sara
A1 González-Juanatey, Carlos
A1 Corrales, Alfonso
A1 Vicente, Esther F
A1 Pulito-Cueto, Verónica
A1 Miranda-Filloy, José A
A1 Ramírez Huaranga, Marco A
A1 Blanco, Ricardo
A1 Robustillo-Villarino, Montserrat
A1 Rodríguez-Carrio, Javier
A1 Alperi-López, Mercedes
A1 Alegre-Sancho, Juan J
A1 Mijares, Verónica
A1 Lera-Gómez, Leticia
A1 Pérez-Pampín, Eva
A1 González, Antonio
A1 Ortega-Castro, Rafaela
A1 López-Pedrera, Chary
A1 García Vivar, Mari L
A1 Gómez-Arango, Catalina
A1 Raya, Enrique
A1 Narvaez, Javier
A1 Balsa, Alejandro
A1 López-Longo, Francisco J
A1 Carreira, Patricia
A1 González-Álvaro, Isidoro
A1 Rodríguez-Rodríguez, Luis
A1 Fernández-Gutiérrez, Benjamín
A1 Ferraz-Amaro, Iván
A1 Gualillo, Oreste
A1 Castañeda, Santos
A1 Martín, Javier
A1 Llorca, Javier
A1 González-Gay, Miguel A
AB To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA). 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. A genetic variant of the RARB gene (rs116199914) was associated with CIMT values at the genome-wide level of significance (minor allele [G] β coefficient 0.142, P = 1.86 × 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 × 10-3 ). Furthermore, our data suggest potential influences of the previously described candidate CV risk loci NFKB1, MSRA, and ZC3HC1 (P = 8.12 × 10-4 , P = 5.94 × 10-4 , and P = 2.46 × 10-4 , respectively). The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA.
YR 2019
FD 2019-01-18
LK http://hdl.handle.net/10668/12993
UL http://hdl.handle.net/10668/12993
LA en
DS RISalud
RD Apr 12, 2025