@article{10902/16985,
year = {2019},
month = {3},
url = {http://hdl.handle.net/10902/16985},
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.},
organization = {This study was supported by European Union FEDER funds and “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060 and PI15/00525) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 and RD16/0012 (RIER) from ISCIII, and in part by grants from the European IMI BTCure Program. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, “Investing in your future”) (grant CP16/00033). FDC was supported by the “Ramón y Cajal” programme of the Spanish Ministry of Economy and Competitiveness through the grant RYC-2014-16458. FG is a recipient of a Sara Borrell post-doctoral fellowship from the ISCIII, co-funded by the ESF (grant CD15/00095). SR-M is supported by funds of the RETICS Program (RIER) RD16/0012/0009 (ISCIII, co-funded by ERDF). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ERDF).},
publisher = {John Wiley and Sons Ltd},
publisher = {Arthritis Rheumatol. 2019 Mar;71(3):351-360},
title = {Identification of a 3'-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study},
author = {López Mejías, Raquel and Carmona, F. David and Genre, Fernanda and Remuzgo Martínez, Sara and González-Juanatey, Carlos and Corrales Martínez, Alfonso and Vicente, Esther F. and Pulito Cueto, Verónica and Miranda-Filloy, José A. and Ramírez Huaranga, Marco A. and Blanco Alonso, Ricardo and Robustillo-Villarino, Montserrat and Rodríguez-Carrio, Javier and Alperi-López, Mercedes and Alegre-Sancho, Juan J. and Mijares Díaz, Verónica and Lera-Gómez, Leticia and Llorca Díaz, Francisco Javier and González-Gay Mantecón, Miguel Ángel and Pérez-Pampín, Eva},
}