%0 Journal Article
%A López-Mejías, Raquel
%A Carmona, F David
%A Genre, Fernanda
%A Remuzgo-Martínez, Sara
%A González-Juanatey, Carlos
%A Corrales, Alfonso
%A Vicente, Esther F
%A Pulito-Cueto, Verónica
%A Miranda-Filloy, José A
%A Ramírez Huaranga, Marco A
%A Blanco, Ricardo
%A Robustillo-Villarino, Montserrat
%A Rodríguez-Carrio, Javier
%A Alperi-López, Mercedes
%A Alegre-Sancho, Juan J
%A Mijares, Verónica
%A Lera-Gómez, Leticia
%A Pérez-Pampín, Eva
%A González, Antonio
%A Ortega-Castro, Rafaela
%A López-Pedrera, Chary
%A García Vivar, Mari L
%A Gómez-Arango, Catalina
%A Raya, Enrique
%A Narvaez, Javier
%A Balsa, Alejandro
%A López-Longo, Francisco J
%A Carreira, Patricia
%A González-Álvaro, Isidoro
%A Rodríguez-Rodríguez, Luis
%A Fernández-Gutiérrez, Benjamín
%A Ferraz-Amaro, Iván
%A Gualillo, Oreste
%A Castañeda, Santos
%A Martín, Javier
%A Llorca, Javier
%A González-Gay, Miguel A
%T Identification of a 3'-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study.
%D 2019
%U http://hdl.handle.net/10668/12993
%X 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.
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