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...
Main Authors: | , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
id |
doaj-272715cbf08d4a5783bf93c6a652df4f |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT mercedesgarciabermudez smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT raquellopezmejias smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT fernandagenre smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT santoscastaneda smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT carlosgonzalezjuanatey smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT javierllorca smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT alfonsocorrales smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT joseamirandafilloy smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT javierruedagotor smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT carmengomezvaquero smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT luisrodriguezrodriguez smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT benjaminfernandezgutierrez smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT dorapascualsalcedo smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT alejandrobalsa smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT franciscojlopezlongo smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT patriciacarreira smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT ricardoblanco smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT isidorogonzalezalvaro smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT javiermartin smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients AT miguelagonzalezgay smad3rs17228212genepolymorphismisassociatedwithreducedrisktocerebrovascularaccidentsandsubclinicalatherosclerosisinanticcpnegativespanishrheumatoidarthritispatients |
_version_ |
1725136155497725952 |