CCR5Δ32 variant and cardiovascular disease in patients with rheumatoid arthritis: a cohort study

Arthritis Research & Therapy

Luis Rodríguez-Rodríguez⁴  Carlos González-Juanatey⁵  Mercedes García-Bermúdez²  Tomas R Vázquez-Rodríguez¹  Jose A Miranda-Filloy¹  Benjamin Fernández-Gutiérrez⁴  Javier Llorca³  Javier Martin²  Miguel A González-Gay⁶ 

[1] Division of Rheumatology, Hospital Xeral-Calde, c/Dr. Ochoa s/n, Lugo E-27004, Spain

[2] Instituto de Parasitología y Biomedicina López-Neyra, C.S.I.C., Parque Tecnológico de Ciencias de la Salud, Avenida del Conocimiento s/n Armilla, Granada E-18100, Spain

[3] Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, IFIMAV, and CIBER Epidemiología y Salud Pública (CIBERESP), Avenida Herrera Oria s/n, E-39011 Santander, Spain

[4] Division of Rheumatology, Hospital Clinico San Carlos, c/Profesor Martín Lagos, s/n Madrid E-28040, Spain

[5] Division of Cardiology, Hospital Xeral-Calde, c/Dr.Ochoa s/n, Lugo E-27004, Spain

[6] Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, IFIMAV, Avenida de Valdecilla s/n, E-39008, Santander, Spain

关键词: rs333;    CCR5Δ32;    genetics;    cardiovascular disease;    atherosclerosis;    rheumatoid arthritis;   

Others  :  1098585
DOI  :  10.1186/ar3444

 received in 2011-02-28, accepted in 2011-08-16,  发布年份 2011

【 摘 要 】

Introduction

The aim of our study was to analyze the influence of the CCR5Δ32 polymorphism in the risk of cardiovascular (CV) events and subclinical atherosclerosis among patients with rheumatoid arthritis (RA).

Methods

A total of 645 patients fulfilling the American Rheumatism Association 1987 revised classification criteria for RA were studied. Patients were genotyped for the CCR5 rs333 polymorphism using predesigned TaqMan assays. Also, HLA DRB1 genotyping was performed using molecular-based methods. Carotid intima-media thickness, flow-mediated endothelium-dependent dilatation (FMD) and endothelium-independent vasodilatation, which were used as surrogate markers of subclinical atherosclerosis, were measured in a subgroup of patients with no clinical CV disease.

Results

A lower frequency of carriers of the CCR5Δ32 allele among patients with CV events (3.4% versus 11.3%, P = 0.025, odds ratio 0.28, 95% confidence interval (95% CI) 0.06 to 0.89) was observed. However, after adjusting for gender, age at time of RA diagnosis, and the presence of shared epitope, rheumatoid factor and classic CV risk factors in the Cox regression analysis, this reduction of CV events in CCR5Δ32 allele carriers was slightly outside the range of significance (P = 0.097; hazard ratio 0.37 (95% CI 0.12 to 1.19)). Carriers of the CCR5Δ32 deletion also showed higher FMD values than the remaining patients (CCR5/CCR5Δ32 patients: 7.03% ± 6.61% versus CCR5/CCR5 patients: 5.51% ± 4.66%). This difference was statistically significant when analysis of covariance was performed (P = 0.024).

Conclusions

Our results show a potential influence of the CCR5Δ32 deletion on the risk of CV disease among patients with RA. This may be due to a protective effect of this allelic variant against the development of vascular endothelial dysfunction.

【 授权许可】

   
2011 Rodríguez-Rodríguez et al.; licensee BioMed Central Ltd.

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