[Clinical and genetic associations in patients with non-cardioembolic ischemic stroke]

To study the associations of genetic markers influencing the residual reactivity of platelets during antiplatelet therapy with acetylsalicylic acid, and clinical and laboratory parameters, including parameters of the platelet hemostasis, in patients with non-cardioembolic ischemic stroke (IS) for a deeper understanding of the pathogenetic mechanisms and prediction of response to therapy and clinical outcome.

The study included 296 patients (average age 64.65 [55; 76] years) undergoing treatment at the City Clinical Hospital named after. N.I. Pirogov: 98 patients with atherothrombotic IS and 196 with an unspecified pathogenetic variant of IS according to TOAST criteria. The US National Institutes of Health Stroke Severity Scale (NIHSS) was used. NIHSS scores at discharge (3 [2;7]) were significantly lower than scores at admission - 9 [6;14] (p<0.0005). Associations of ITGB3, GPIba, TBXA2R, ITGA2, PLA2G7, HMOX1, PTGS1, PTGS2, ADRA2A, ABCB1, PEAR1 polymorphisms and the intergenic region 9p21.3 with clinical and laboratory parameters were studied.

In the group with atherothrombotic variant of IS, ITGA2 rs1126643 and HMOX1 rs2071746 polymorphisms were associated with the degree of carotid artery stenosis, and TBXA2R rs4523 and PTGS2 rs689466 polymorphisms were associated with triglyceride levels. Associations between ITGA2 rs1062535 polymorphism and adenosine diphosphate (ADP)-induced platelet aggregation (PA), PLA2G7 rs1051931 polymorphism and collagen-induced PA as well as PEAR1 rs12041331 polymorphism and ristomycin-induced PA were identified. In patients with unspecified IS, ITGB3 rs5918 polymorphism was associated with adrenaline-induced PA; TBXA2R rs4523 with ADP-induced PA; ADRA2A rs4311994 was associated with arachidonic acid-induced PA; ITGA2 rs1062535 with ristomycin-induced PA and spontaneous aggregation (SA). Also, the SA level was affected by polymorphisms PLA2G7 rs1051931, 9p21.3 rs10120688, ABCB1 rs1045642 and ITGA2 rs1062535 was associated with the dynamics of NIHSS.

The results can be used to develop personalized approaches to secondary prevention of IS, including the selection of individual antiplatelet therapy.