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Identification of a 3'-untranslated genetic variant of RARB associated with carotid intima-media thickness in rheumatoid arthritis: a genome-wide association study

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] ? 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). CONCLUSION: The present findings strongly suggest that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Autoría: López-Mejías R., Carmona F.D., Genre F., Remuzgo-Martínez S., González-Juanatey C., Corrales A., Vicente E.F., Pulito-Cueto V., Miranda-Filloy J.A., 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 E., 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., Ca

 Fuente: Arthritis and Rheumatology, 2019, 71(3), 351-360

Editorial: John Wiley and Sons Ltd

 Fecha de publicación: 01/03/2019

Nº de páginas: 10

Tipo de publicación: Artículo de Revista

 DOI: 10.1002/art.40734

ISSN: 2326-5205,2326-5191

Url de la publicación: https://www.doi.org/10.1002/art.40734

Autoría

LÓPEZ MEJÍAS, RAQUEL

CARMONA, F. DAVID

FERNANDA GENRE

REMUZGO-MARTÍNEZ, SARA

GONZÁLEZ-JUANATEY, CARLOS

ALFONSO FERNANDO CORRALES MARTINEZ

VICENTE, ESTHER F.

VERONICA PULITO CUETO

MIRANDA-FILLOY, JOSÉ A.

RAMÍREZ HUARANGA, MARCO A.

ROBUSTILLO-VILLARINO, MONTSERRAT

RODRÍGUEZ-CARRIO, JAVIER

ALPERI-LÓPEZ, MERCEDES

ALEGRE-SANCHO, JUAN J.

VERONICA MIJARES DIAZ

LERA-GÓMEZ, LETICIA

PÉREZ-PAMPÍN, EVA

FRANCISCO JAVIER LLORCA DIAZ