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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
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 acro...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590191/ https://www.ncbi.nlm.nih.gov/pubmed/30251476 http://dx.doi.org/10.1002/art.40734 |
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author | López‐Mejías, Raquel Carmona, F. David Genre, Fernanda Remuzgo‐Martínez, Sara González‐Juanatey, Carlos Corrales, Alfonso Vicente, Esther F. Pulito‐Cueto, Verónica Miranda‐Filloy, José A. Ramírez Huaranga, Marco A. Blanco, Ricardo Robustillo‐Villarino, Montserrat Rodríguez‐Carrio, Javier Alperi‐López, Mercedes Alegre‐Sancho, Juan J. Mijares, Verónica Lera‐Gómez, Leticia Pérez‐Pampín, Eva González, Antonio Ortega‐Castro, Rafaela López‐Pedrera, Chary García Vivar, Mari L. Gómez‐Arango, Catalina Raya, Enrique Narvaez, Javier Balsa, Alejandro López‐Longo, Francisco J. Carreira, Patricia González‐Álvaro, Isidoro Rodríguez‐Rodríguez, Luis Fernández‐Gutiérrez, Benjamín Ferraz‐Amaro, Iván Gualillo, Oreste Castañeda, Santos Martín, Javier Llorca, Javier González‐Gay, Miguel A. |
author_facet | López‐Mejías, Raquel Carmona, F. David Genre, Fernanda Remuzgo‐Martínez, Sara González‐Juanatey, Carlos Corrales, Alfonso Vicente, Esther F. Pulito‐Cueto, Verónica Miranda‐Filloy, José A. Ramírez Huaranga, Marco A. Blanco, Ricardo Robustillo‐Villarino, Montserrat Rodríguez‐Carrio, Javier Alperi‐López, Mercedes Alegre‐Sancho, Juan J. Mijares, Verónica Lera‐Gómez, Leticia Pérez‐Pampín, Eva González, Antonio Ortega‐Castro, Rafaela López‐Pedrera, Chary García Vivar, Mari L. Gómez‐Arango, Catalina Raya, Enrique Narvaez, Javier Balsa, Alejandro López‐Longo, Francisco J. Carreira, Patricia González‐Álvaro, Isidoro Rodríguez‐Rodríguez, Luis Fernández‐Gutiérrez, Benjamín Ferraz‐Amaro, Iván Gualillo, Oreste Castañeda, Santos Martín, Javier Llorca, Javier González‐Gay, Miguel A. |
author_sort | López‐Mejías, Raquel |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6590191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65901912019-07-08 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 Carmona, F. David Genre, Fernanda Remuzgo‐Martínez, Sara González‐Juanatey, Carlos Corrales, Alfonso Vicente, Esther F. Pulito‐Cueto, Verónica Miranda‐Filloy, José A. Ramírez Huaranga, Marco A. Blanco, Ricardo Robustillo‐Villarino, Montserrat Rodríguez‐Carrio, Javier Alperi‐López, Mercedes Alegre‐Sancho, Juan J. Mijares, Verónica Lera‐Gómez, Leticia Pérez‐Pampín, Eva González, Antonio Ortega‐Castro, Rafaela López‐Pedrera, Chary García Vivar, Mari L. Gómez‐Arango, Catalina Raya, Enrique Narvaez, Javier Balsa, Alejandro López‐Longo, Francisco J. Carreira, Patricia González‐Álvaro, Isidoro Rodríguez‐Rodríguez, Luis Fernández‐Gutiérrez, Benjamín Ferraz‐Amaro, Iván Gualillo, Oreste Castañeda, Santos Martín, Javier Llorca, Javier González‐Gay, Miguel A. Arthritis Rheumatol Rheumatoid Arthritis 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. John Wiley and Sons Inc. 2019-01-18 2019-03 /pmc/articles/PMC6590191/ /pubmed/30251476 http://dx.doi.org/10.1002/art.40734 Text en © 2018 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Rheumatoid Arthritis López‐Mejías, Raquel Carmona, F. David Genre, Fernanda Remuzgo‐Martínez, Sara González‐Juanatey, Carlos Corrales, Alfonso Vicente, Esther F. Pulito‐Cueto, Verónica Miranda‐Filloy, José A. Ramírez Huaranga, Marco A. Blanco, Ricardo Robustillo‐Villarino, Montserrat Rodríguez‐Carrio, Javier Alperi‐López, Mercedes Alegre‐Sancho, Juan J. Mijares, Verónica Lera‐Gómez, Leticia Pérez‐Pampín, Eva González, Antonio Ortega‐Castro, Rafaela López‐Pedrera, Chary García Vivar, Mari L. Gómez‐Arango, Catalina Raya, Enrique Narvaez, Javier Balsa, Alejandro López‐Longo, Francisco J. Carreira, Patricia González‐Álvaro, Isidoro Rodríguez‐Rodríguez, Luis Fernández‐Gutiérrez, Benjamín Ferraz‐Amaro, Iván Gualillo, Oreste Castañeda, Santos Martín, Javier Llorca, Javier González‐Gay, Miguel A. Identification of a 3′‐Untranslated Genetic Variant of RARB Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study |
title | Identification of a 3′‐Untranslated Genetic Variant of RARB Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study |
title_full | Identification of a 3′‐Untranslated Genetic Variant of RARB Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study |
title_fullStr | Identification of a 3′‐Untranslated Genetic Variant of RARB Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study |
title_full_unstemmed | Identification of a 3′‐Untranslated Genetic Variant of RARB Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study |
title_short | Identification of a 3′‐Untranslated Genetic Variant of RARB Associated With Carotid Intima‐Media Thickness in Rheumatoid Arthritis: A Genome‐Wide Association Study |
title_sort | identification of a 3′‐untranslated genetic variant of rarb associated with carotid intima‐media thickness in rheumatoid arthritis: a genome‐wide association study |
topic | Rheumatoid Arthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590191/ https://www.ncbi.nlm.nih.gov/pubmed/30251476 http://dx.doi.org/10.1002/art.40734 |
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