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

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 acro...

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Autores: López-Mejías, R., Carmona, F. D., Genre, F., Remuzgo-Martínez, S., González Juanatey, Carlos, Corrales, A., Vicente, E. F., Pulito-Cueto, V., Miranda Filloy, José Alberto, Ramírez Huaranga, M. A., Blanco, R., Robustillo-Villarino, M., Rodríguez-Carrio, J., Alperi-López, M., Alegre-Sancho, J. J., Mijares, V., Lera-Gómez, L., Pérez Pampín, Eva, González, A., Ortega-Castro, R., López-Pedrera, C., García Vivar, M. L., Gómez-Arango, C., Raya, E., Narvaez, J., Balsa, A., López-Longo, F. J., Carreira, P., González-Álvaro, I., Rodríguez-Rodríguez, L., Fernández-Gutiérrez, B., Ferraz-Amaro, I., Gualillo ., Oreste, Castañeda, S., Martín, J., Llorca, J., González-Gay, M. A.
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/15494
Acceso en línea:https://www.ncbi.nlm.nih.gov/pubmed/30251476
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590191/pdf/ART-71-351.pdf
http://hdl.handle.net/20.500.11940/15494
Access Level:acceso abierto
Palabra clave:CHUS
HULA
IDIS
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Sumario: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.

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