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Title

SMAD3 rs17228212 Gene Polymorphism Is Associated with Reduced Risk to Cerebrovascular Accidents and Subclinical Atherosclerosis in Anti-CCP Negative Spanish Rheumatoid Arthritis Patients

AuthorsGarcía-Bermúdez, M.; López-Mejías, Raquel; Genre, Fernanda; Castañeda, Santos; González-Juanatey, Carlos; Llorca, Javier; Corrales, Alfonso; Miranda-Filloy, J. A.; Rueda-Gotor, Javier; Gómez-Vaquero, C.; Rodríguez-Rodríguez, Luis; Fernández-Gutiérrez, B.; Pascual-Salcedo, Dora; Balsa, Alejandro; López-Longo, Francisco Javier; Carreira, P.; Blanco, Ricardo; González-Álvaro, I.; Martín, J.; González-Gay, M. A.
Issue Date21-Oct-2013
PublisherPublic Library of Science
CitationPLoS ONE
AbstractRheumatoid 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.
DescriptionFormal Correction: Errors in Affiliations Posted by PLoS_ONE_Group on 08 Nov 2013 at 00:16 GMT Affiliation number 10 for the 15th author is incorrect. The correct affiliation is: Department of Rheumatology, Hospital Universitario Gregorio Marañón, Madrid, Spain. In addition, affiliation number 11 for the 16th author is incorrect. The correct affiliation is: Department of Rheumatology, Hospital Universitario 12 de Octubre, Madrid, Spain. No competing interests declared. Citation: García-Bermúdez M, López-Mejías R, Genre F, Castañeda S, González-Juanatey C, et al. (2013) 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: http://dx.doi.org/10.1371/annotation/3fc037c1-2585-4d2b-a781-e04ab7b3bfeb
Publisher version (URL)http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0077695
DOI: 10.1371/journal.pone.0077695
URIhttp://hdl.handle.net/10261/87150
DOI10.1371/journal.pone.0077695
E-ISSN1932-6203
Appears in Collections:(IPBLN) Artículos
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