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Title

Identification of a 3 '-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study

AuthorsLópez-Mejías, Raquel; Carmona, F. D.; Genre, Fernanda; Remuzgo-Martínez, Sara; González-Juanatey, Carlos; Corrales, Alfonso; Vicente, Esther; Pulito-Cueto, Veronica; Miranda-Filloy, J. A.; Ramírez Huaranga, Marco A.; Blanco, Ricardo; Robustillo-Villarino, Montserrat; Rodríguez-Carrio, Javier; Alperi-López, M.; Alegre-Sancho, Juan-José; Mijares, Verónica; Lera-Gómez, Leticia; Pérez-Pampin, Eva; González, Antonio; Ortega-Castro, Rafaela; López-Pedrera, Chary; García Vivar, Mari L.; Gómez-Arango, Catalina; Raya, Enrique; Narváez, Javier; Balsa, Alejandro; Lpez-Longo, Francisco Javier; Carreira, P.; González-Álvaro, I.; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, B.; Ferraz-Amaro, Iván; Gualillo, Oreste; Castañeda, Santos; Martín, J.; Llorca, Javier; González-Gay, M. A
Issue DateMar-2019
PublisherJohn Wiley & Sons
CitationArthritis and Rheumatology
AbstractObjective 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.
URIhttp://hdl.handle.net/10261/190701
DOIhttp://dx.doi.org/10.1002/art.40734
ISSN2326-5191
E-ISSN2326-5205
Appears in Collections:(IPBLN) Artículos
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