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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Identification of a 3′-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study
Arthritis and Rheumatology, Volume 71, No. 3, Year 2019
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Description
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] β 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. © 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC6590191/bin/ART-71-351-s001.docx
Authors & Co-Authors
López-Mejías, Raquel
Unknown Affiliation
Carmona, Francisco David
Spain, Granada
Universidad de Granada
Genre, Fernanda
Unknown Affiliation
Remuzgo-Martínez, Sara
Unknown Affiliation
González-Juanatey, Carlos
Spain, Lugo
Hospital Universitario Lucus Augusti
Corrales, Alfonso F.
Unknown Affiliation
Vicente-Rabaneda, Esther Francisca
Spain, Madrid
Hospital Universitario de la Princesa
Pulito-Cueto, Verónica Bsc
Unknown Affiliation
Miranda-Filloy, José Alberto
Spain, Lugo
Hospital Universitario Lucus Augusti
Ramírez-Huaranga, Marco Aurelio
Spain, Ciudad Real
Hospital General de Ciudad Real
Blanco-Alonso, Ricardo
Unknown Affiliation
Robustillo-Villarino, Montserrat
Unknown Affiliation
Rodríguez-Carrio, Javier
Spain, Oviedo
Hospital Universitario Central de Asturias
Alperi-López, Mercedes
Spain, Oviedo
Instituto de Investigación Sanitaria Del Principado de Asturias
Alegre-Sancho, Juan José
Spain, Valencia
Hospital Universitario Dr. Peset
Mijares, Verónica
Unknown Affiliation
Lera-Gómez, Leticia
Unknown Affiliation
Ortega-Castro, Rafaela
Spain, Cordoba
Universidad de Córdoba
García-Vivar, María Luz
Spain, Bilbao
Osakidetza, Basurto University Hospital
Raya Álvarez, Enriqué G.
Spain, Granada
Hospital Universitario San Cecilio
Narváez, Javier A.
Spain, Barcelona
Hospital Universitari de Bellvitge
Balsa, Alejando
Spain, Madrid
Hospital Universitario la Paz
López-Longo, Francisco Javier
Spain, Madrid
Hospital General Universitario Gregorio Marañón
Carreira-Delgado, Patricia E.
Spain, Madrid
Hospital Universitario 12 de Octubre
Rodríguez-Rodríguez, Luís Pablo
Spain, Madrid
Hospital Clínico San Carlos
Fernàndez-Gutiérrez, Benjamín
Spain, Madrid
Hospital Clínico San Carlos
Ferraz-Amaro, Iván
Spain, Santa Cruz de Tenerife
Hospital Universitario de Canarias
Gualillo, O.
Spain, Santiago de Compostela
Hospital Clínico Universitario de Santiago
Castañeda, Santos
Spain, Madrid
Hospital Universitario de la Princesa
Martin, Javier
Spain, Armilla
Csic - Instituto de Parasitologia y Biomedicina Lopez Neyra Ipbln
Llorca-Díaz, Javier Francisco
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
González-Gay, Miguel Ángel
South Africa, Johannesburg
University of the Witwatersrand
Statistics
Citations: 24
Authors: 32
Affiliations: 20
Identifiers
Doi:
10.1002/art.40734
ISSN:
23265191
Research Areas
Genetics And Genomics
Noncommunicable Diseases