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.
Arthritis Res Ther. 2011 Aug 16;13(4):R133. doi: 10.1186/ar3444.
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).
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.
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).
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.
我们研究的目的是分析 CCR5Δ32 多态性在类风湿关节炎（RA）患者心血管（CV）事件和亚临床动脉粥样硬化风险中的影响。
共研究了 645 名符合美国风湿病学会 1987 年修订的 RA 分类标准的患者。使用预设计的 TaqMan 检测法对患者进行 CCR5 rs333 多态性基因分型。此外，还使用基于分子的方法对 HLA-DRB1 基因分型进行了检测。在没有临床 CV 疾病的患者亚组中测量了作为亚临床动脉粥样硬化替代标志物的颈动脉内膜中层厚度、血流介导的内皮依赖性舒张（FMD）和内皮非依赖性血管舒张。
在发生 CV 事件的患者中，CCR5Δ32 等位基因携带者的频率较低（3.4%对 11.3%，P=0.025，优势比 0.28，95%置信区间（95%CI）0.06 至 0.89）。然而，在 Cox 回归分析中，在校正性别、RA 诊断时的年龄以及共同表位、类风湿因子和经典 CV 危险因素后，CCR5Δ32 等位基因携带者的 CV 事件减少幅度略低于显著水平（P=0.097；风险比 0.37（95%CI 0.12 至 1.19））。CCR5Δ32 缺失的携带者的 FMD 值也高于其余患者（CCR5/CCR5Δ32 患者：7.03%±6.61%对 CCR5/CCR5 患者：5.51%±4.66%）。当进行协方差分析时，这种差异具有统计学意义（P=0.024）。
我们的结果表明 CCR5Δ32 缺失可能对 RA 患者的 CV 疾病风险有潜在影响。这可能是由于该等位基因变异对血管内皮功能障碍的发展具有保护作用。
