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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.

SUBMITTER: Lopez-Mejias R 

PROVIDER: S-EPMC6590191 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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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.

López-Mejías Raquel R   Carmona F David FD   Genre Fernanda F   Remuzgo-Martínez Sara S   González-Juanatey Carlos C   Corrales Alfonso A   Vicente Esther F EF   Pulito-Cueto Verónica V   Miranda-Filloy José A JA   Ramírez Huaranga Marco A MA   Blanco Ricardo R   Robustillo-Villarino Montserrat M   Rodríguez-Carrio Javier J   Alperi-López Mercedes M   Alegre-Sancho Juan J JJ   Mijares Verónica V   Lera-Gómez Leticia L   Pérez-Pampín Eva E   González Antonio A   Ortega-Castro Rafaela R   López-Pedrera Chary C   García Vivar Mari L ML   Gómez-Arango Catalina C   Raya Enrique E   Narvaez Javier J   Balsa Alejandro A   López-Longo Francisco J FJ   Carreira Patricia P   González-Álvaro Isidoro I   Rodríguez-Rodríguez Luis L   Fernández-Gutiérrez Benjamín B   Ferraz-Amaro Iván I   Gualillo Oreste O   Castañeda Santos S   Martín Javier J   Llorca Javier J   González-Gay Miguel A MA  

Arthritis & rheumatology (Hoboken, N.J.) 20190118 3


<h4>Objective</h4>To investigate the genetic background influencing the development of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA).<h4>Methods</h4>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 pr  ...[more]

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