OBJECTIVE
To study the effect of CCR5 rs746492 genetic variants on the results of percutaneous coronary interventions (PCI), humoral markers of inflammation, endothelial dysfunction and platelet-vascular hemostasis in patients with coronary artery disease (CAD).
MATERIAL AND METHODS
The study included 84 patients with stable CAD who underwent elective PCI. Mean age of patients was 57.2±2.1 years. Analysis was carried out in 3 groups: group 1 (19 patients) — AA rs746492 CCR5 genotype carriers, group 2 (41 patients) — AG rs746492 CCR5 genotype carriers, group 3 (24 patients) — GG rs746492 CCR5 genotype carriers.
RESULTS
CCR5 rs746492 gene polymorphism (GG genotype) affects humoral markers of inflammatory response (serum CRP increase within 6 months after PCI), endothelial dysfunction (increased expression of sVCAM-1 within 6 months after PCI, higher activity of von Willebrand factor after PCI). This polymorphism is associated with lower resistance to thrombosis (reduced activity of antithrombin-III and protein C) and high residual platelet reactivity under dual antiplatelet therapy (DAPT). We established predictive value for the following factors: CRP >0.5 mg/dl within 6 months after PCI (OR 3.92; 95% CI 1.39—11.0), high platelet reactivity under DAPT a month after PCI (OR 2.75; 95% CI 1.03—7.35), high platelet reactivity under DAPT a year after PCI (OR 3.33; 95% CI 1.03—10.83), reduced activity of antithrombin-III within 6 months after PCI (OR 9.0; 95% CI 1.33—61.14), carriage of GG rs746492 genotype of CCR5 chemokine receptor gene (OR 3.55; 95% CI 1.31—9.57).
CONCLUSION
The influence of chemokine receptor gene CCR5 rs746492 polymorphism is multifunctional and involves various pathophysiological processes: inflammation, endothelial dysfunction, clotting, platelet-vascular hemostasis, proliferation, lipid metabolism disorders. The last ones are essential for thrombosis, stent restenosis and further progression of coronary atherosclerosis.
