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

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

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Autores de IDIVAL

Autores ajenos al IDIVAL

  • Carmona FD
  • Remuzgo-Martinez, Sara
  • Gonzalez-Juanatey, Carlos
  • Vicente, Esther F.
  • Pulito-Cueto, Veronica
  • Miranda-Filloy, Jose A.
  • Ramirez Huaranga, Marco A.
  • Robustillo-Villarino, Montserrat
  • Rodriguez-Carrio, Javier
  • Alperi-Lopez, Mercedes
  • Alegre-Sancho, Juan J.
  • Mijares, Veronica
  • Lera-Gomez, Leticia
  • Perez-Pampin, Eva
  • Gonzalez, Antonio
  • Ortega-Castro, Rafaela
  • Lopez-Pedrera, Chary
  • Garcia Vivar, Mari L.
  • Gomez-Arango, Catalina
  • Raya, Enrique
  • Narvaez, Javier
  • Balsa, Alejandro
  • Lopez-Longo, Francisco J.
  • Carreira, Patricia
  • Gonzalez-Alvaro, Isidoro
  • Rodriguez-Rodriguez, Luis
  • Fernandez-Gutierrez, Benjamin
  • Ferraz-Amaro, Ivan
  • Gualillo, Oreste
  • Castañeda S
  • Martin, Javier
  • Llorca, Javier
  • Gonzalez-Gay, Miguel A.

Unidades

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] 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.

© 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Datos de la publicación

ISSN/ISSNe:
2326-5191, 2326-5205

Arthritis & Rheumatology  WILEY-BLACKWELL

Tipo:
Article
Páginas:
351-360

Citas Recibidas en Web of Science: 25

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