SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.

UNLABELLED:Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with...

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Main Authors: Mercedes García-Bermúdez, Raquel López-Mejías, Fernanda Genre, Santos Castañeda, Carlos González-Juanatey, Javier Llorca, Alfonso Corrales, José A Miranda-Filloy, Javier Rueda-Gotor, Carmen Gómez-Vaquero, Luis Rodríguez-Rodríguez, Benjamín Fernández-Gutiérrez, Dora Pascual-Salcedo, Alejandro Balsa, Francisco J López-Longo, Patricia Carreira, Ricardo Blanco, Isidoro González-Álvaro, Javier Martín, Miguel A González-Gay
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3804609?pdf=render
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spelling doaj-272715cbf08d4a5783bf93c6a652df4f2020-11-25T01:19:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7769510.1371/journal.pone.0077695SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.Mercedes García-BermúdezRaquel López-MejíasFernanda GenreSantos CastañedaCarlos González-JuanateyJavier LlorcaAlfonso CorralesJosé A Miranda-FilloyJavier Rueda-GotorCarmen Gómez-VaqueroLuis Rodríguez-RodríguezBenjamín Fernández-GutiérrezDora Pascual-SalcedoAlejandro BalsaFrancisco J López-LongoPatricia CarreiraRicardo BlancoIsidoro González-ÁlvaroJavier MartínMiguel A González-GayUNLABELLED:Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA. METHODS:One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography. RESULTS:No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14-0.94], p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients. CONCLUSIONS:Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have importance to establish predictive models of CV disease in RA patients according to anti-CCP status.http://europepmc.org/articles/PMC3804609?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Mercedes García-Bermúdez
Raquel López-Mejías
Fernanda Genre
Santos Castañeda
Carlos González-Juanatey
Javier Llorca
Alfonso Corrales
José A Miranda-Filloy
Javier Rueda-Gotor
Carmen Gómez-Vaquero
Luis Rodríguez-Rodríguez
Benjamín Fernández-Gutiérrez
Dora Pascual-Salcedo
Alejandro Balsa
Francisco J López-Longo
Patricia Carreira
Ricardo Blanco
Isidoro González-Álvaro
Javier Martín
Miguel A González-Gay
spellingShingle Mercedes García-Bermúdez
Raquel López-Mejías
Fernanda Genre
Santos Castañeda
Carlos González-Juanatey
Javier Llorca
Alfonso Corrales
José A Miranda-Filloy
Javier Rueda-Gotor
Carmen Gómez-Vaquero
Luis Rodríguez-Rodríguez
Benjamín Fernández-Gutiérrez
Dora Pascual-Salcedo
Alejandro Balsa
Francisco J López-Longo
Patricia Carreira
Ricardo Blanco
Isidoro González-Álvaro
Javier Martín
Miguel A González-Gay
SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.
PLoS ONE
author_facet Mercedes García-Bermúdez
Raquel López-Mejías
Fernanda Genre
Santos Castañeda
Carlos González-Juanatey
Javier Llorca
Alfonso Corrales
José A Miranda-Filloy
Javier Rueda-Gotor
Carmen Gómez-Vaquero
Luis Rodríguez-Rodríguez
Benjamín Fernández-Gutiérrez
Dora Pascual-Salcedo
Alejandro Balsa
Francisco J López-Longo
Patricia Carreira
Ricardo Blanco
Isidoro González-Álvaro
Javier Martín
Miguel A González-Gay
author_sort Mercedes García-Bermúdez
title SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.
title_short SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.
title_full SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.
title_fullStr SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.
title_full_unstemmed SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-CCP negative Spanish rheumatoid arthritis patients.
title_sort smad3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents and subclinical atherosclerosis in anti-ccp negative spanish rheumatoid arthritis patients.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description UNLABELLED:Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA. METHODS:One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography. RESULTS:No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14-0.94], p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients. CONCLUSIONS:Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have importance to establish predictive models of CV disease in RA patients according to anti-CCP status.
url http://europepmc.org/articles/PMC3804609?pdf=render
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