2024-03-28T14:54:32Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/871502019-10-10T13:45:46Zcom_10261_64com_10261_1col_10261_317
00925njm 22002777a 4500
dc
García-Bermúdez, M.
author
López-Mejías, Raquel
author
Genre, Fernanda
author
Castañeda, Santos
author
González-Juanatey, Carlos
author
Llorca, Javier
author
Corrales, Alfonso
author
Miranda-Filloy, J. A.
author
Rueda-Gotor, Javier
author
Gómez-Vaquero, C.
author
Rodríguez-Rodríguez, Luis
author
Fernández-Gutiérrez, B.
author
Pascual-Salcedo, Dora
author
Balsa, Alejandro
author
López-Longo, Francisco Javier
author
Carreira, P.
author
Blanco, Ricardo
author
González-Álvaro, Isidoro
author
Martín, J.
author
González-Gay, M. A.
author
2013-10-21
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.
PLoS ONE
http://hdl.handle.net/10261/87150
10.1371/journal.pone.0077695
1932-6203
24204921
SMAD3 rs17228212 Gene Polymorphism Is Associated with Reduced Risk to Cerebrovascular Accidents and Subclinical Atherosclerosis in Anti-CCP Negative Spanish Rheumatoid Arthritis Patients