Osteoprotegerin CGA haplotype protection against cerebrovascular complications in anti-CCP negative patients with rheumatoid arthritis

Introduction: rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene wi...

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Detalles Bibliográficos
Autores: Genre, Fernanda, López Mejías, Raquel, García-Bermúdez, Mercedes, Castañeda, Santos, González Juanatey, Carlos, Llorca Díaz, Javier, Corrales, Alfonso, Ubilla, Begoña, Miranda-Filloy, José A., Pina, Trinitario, Gómez Vaquero, Carmen, Rodríguez-Rodríguez, Luis, Fernández-Gutiérrez, Benjamín, Balsa, Alejandro, Pascual-Salcedo, Dora, López Longo, Francisco J., Carreira, Patricia, Blanco, Ricardo, González Álvaro, Isidoro, Martín, Javier, González-Gay, Miguel A.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/119310
Acceso en línea:https://hdl.handle.net/2445/119310
Access Level:acceso abierto
Palabra clave:Malalties cerebrovasculars
Artritis reumatoide
Nucleòtids
Cerebrovascular disease
Rheumatoid arthritis
Nucleotides
Descripción
Sumario:Introduction: rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis. Methods: three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression. Results: no association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31-0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04-0.78; p = 0.022, respectively). Conclusion: our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.

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