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 across...

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Autores: López-Mejías R, Carmona FD, Genre F, Remuzgo-Martínez S, González-Juanatey C, Corrales A, Vicente EF, Pulito-Cueto V, Miranda-Filloy JA, Ramírez Huaranga MA, Blanco R, Robustillo-Villarino M, Rodríguez-Carrio J, Alperi-López M, Alegre-Sancho JJ, Mijares V, Lera-Gómez L, Pérez-Pampín E, González A, Ortega-Castro R, López-Pedrera C, García Vivar ML, Gómez-Arango C, Raya E, Narvaez J, Balsa A, López-Longo FJ, Carreira P, González-Álvaro I, Rodríguez-Rodríguez L, Fernández-Gutiérrez B, Ferraz-Amaro I, Gualillo O, Castañeda S, Martín J, Llorca J, González-Gay MA
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p3176
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/3176
Access Level:acceso abierto
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spelling Identification of a 3 '-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association StudyLópez-Mejías RCarmona FDGenre FRemuzgo-Martínez SGonzález-Juanatey CCorrales AVicente EFPulito-Cueto VMiranda-Filloy JARamírez Huaranga MABlanco RRobustillo-Villarino MRodríguez-Carrio JAlperi-López MAlegre-Sancho JJMijares VLera-Gómez LPérez-Pampín EGonzález AOrtega-Castro RLópez-Pedrera CGarcía Vivar MLGómez-Arango CRaya ENarvaez JBalsa ALópez-Longo FJCarreira PGonzález-Álvaro IRodríguez-Rodríguez LFernández-Gutiérrez BFerraz-Amaro IGualillo OCastañeda SMartín JLlorca JGonzález-Gay MAObjective 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.WILEY2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/3176Arthritis & RheumatologyISSN: 23265191ISSNe: 23265205reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p31762026-06-11T12:45:17Z
dc.title.none.fl_str_mv 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
spellingShingle 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 R
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_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_sort Identification of a 3 '-Untranslated Genetic Variant of RARB Associated With Carotid Intima-Media Thickness in Rheumatoid Arthritis: A Genome-Wide Association Study
dc.creator.none.fl_str_mv López-Mejías R
Carmona FD
Genre F
Remuzgo-Martínez S
González-Juanatey C
Corrales A
Vicente EF
Pulito-Cueto V
Miranda-Filloy JA
Ramírez Huaranga MA
Blanco R
Robustillo-Villarino M
Rodríguez-Carrio J
Alperi-López M
Alegre-Sancho JJ
Mijares V
Lera-Gómez L
Pérez-Pampín E
González A
Ortega-Castro R
López-Pedrera C
García Vivar ML
Gómez-Arango C
Raya E
Narvaez J
Balsa A
López-Longo FJ
Carreira P
González-Álvaro I
Rodríguez-Rodríguez L
Fernández-Gutiérrez B
Ferraz-Amaro I
Gualillo O
Castañeda S
Martín J
Llorca J
González-Gay MA
author López-Mejías R
author_facet López-Mejías R
Carmona FD
Genre F
Remuzgo-Martínez S
González-Juanatey C
Corrales A
Vicente EF
Pulito-Cueto V
Miranda-Filloy JA
Ramírez Huaranga MA
Blanco R
Robustillo-Villarino M
Rodríguez-Carrio J
Alperi-López M
Alegre-Sancho JJ
Mijares V
Lera-Gómez L
Pérez-Pampín E
González A
Ortega-Castro R
López-Pedrera C
García Vivar ML
Gómez-Arango C
Raya E
Narvaez J
Balsa A
López-Longo FJ
Carreira P
González-Álvaro I
Rodríguez-Rodríguez L
Fernández-Gutiérrez B
Ferraz-Amaro I
Gualillo O
Castañeda S
Martín J
Llorca J
González-Gay MA
author_role author
author2 Carmona FD
Genre F
Remuzgo-Martínez S
González-Juanatey C
Corrales A
Vicente EF
Pulito-Cueto V
Miranda-Filloy JA
Ramírez Huaranga MA
Blanco R
Robustillo-Villarino M
Rodríguez-Carrio J
Alperi-López M
Alegre-Sancho JJ
Mijares V
Lera-Gómez L
Pérez-Pampín E
González A
Ortega-Castro R
López-Pedrera C
García Vivar ML
Gómez-Arango C
Raya E
Narvaez J
Balsa A
López-Longo FJ
Carreira P
González-Álvaro I
Rodríguez-Rodríguez L
Fernández-Gutiérrez B
Ferraz-Amaro I
Gualillo O
Castañeda S
Martín J
Llorca J
González-Gay MA
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
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] 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/3176
url https://fisabio.portalinvestigacion.com/publicaciones/3176
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv Arthritis & Rheumatology
ISSN: 23265191
ISSNe: 23265205
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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