Associations between inflammation markers and platelet activation and polymorphic gene variants of hemostasis system and platelet receptors in patients with non-valvular atrial fibrillation

Multiple pathogenetic factors related to activation of blood clotting system and platelet aggregation may significantly contribute to occurrence of thromboembolic complications in cardiac arrhythmias. The relevant studies are closely focused on associations between congenital risk factors of thrombosis, and biomarkers that may be related to pathogenesis of thrombotic events in atrial fibrillation. Our objective was to study the relationships between markers of inflammation and platelet activation with polymorphic variants of genes of the hemostasis system and platelet receptors among patients with non-valvular atrial fibrillation receiving anticoagulant therapy with a history of thrombotic complications, and patients with atrial fibrillation without previous thrombotic complications. The study included 60 patients diagnosed with atrial fibrillation, 21 patients developed thrombotic complications. All patients have provided a written informed consent for inclusion in the study. A diagnostic panel of biomarkers, polymorphic variants of genes and platelet aggregation tests was conducted using the facilities at the Center for Collective Use “Medical Genomics” (Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation). Comparative frequency of polymorphic variants of plasminogen activator inhibitor PAI-1 , platelet collagen receptor ITGA2 , nitric oxide synthase NOS3 , and β-2 adrenergic receptor ADRB2 genes did not show any statistically significant differences between patients with or without thrombotic complications. Meanwhile, we have found a decrease in the levels of α-acid glycoprotein, fetuin A, L-selectin, thrombomodulin and increased in CD40L and platelet factor 4 levels in the group of patients with thrombotic complications, compared with patients without thrombosis. A statistically significant difference was noted in the subgroups with a high-risk genotype of thrombosis. The higher-risk genotypes of PAI-1 and ITGA2 genes in the group with thrombotic complications was associated with increased platelet aggregation activity and increased platelet factor 4 contents. A search for associations between markers of inflammation and platelet activation, and polymorphic variants of hemostasis system genes and platelet receptors showed a link between the high-risk genotypes, increased CD40L, platelet factor 4, and aggregation activity among patients with thrombotic complications.