Influence of ITGA2 gene polymorphism on platelet components of hemostasis in patients with acute coronary syndrom

Abstract

Aim: To study and to estimate the aggregation of platelets as an initial link of hemostasis in patients with ACS depending on ITGA 2 – C 807T gene polymorphism.

Materials and methods: there were examined 72 patients, who were on the treatment in the department of the acute coronary pathology of the clinic ”Pheophanya” and in the department of cardiology of Kyiv railway clinic  № 2: 27 women (37,5 %) and 5 men (62,5 %) 56 - 87 years old (mean age– 68,1±7,34 years). The research included patients with ACS, developed on the background of the hypertonic disease. Based on the results of gene-interrogation and corresponding to the aim of the examination, all patients were divided in three groups: І included 20 patients with (27,8 %) С/С genotype, ІІ group consisted of 29 patients (40,3 %) with С/Т genotype and ІІІ group included 23 patients (31,9 %) with Т/Т genotype. At the examination of patients was used the algorithm standard thematic card that included the sections of anamnesis, general clinical, instrumental and laboratory study.

The study of hemostatic parameters in venous blood was carried out immediately at a patient’s admission in hospital. The study of the functional activity of platelets was realized at a laser aggregometer Biola Aggregation Analyser with the computer analysis of curves of light-transmission and features of platelet aggregates. At that there was studied the presence of spontaneous platelets aggregation and stimulated aggregation with inductors: arachidonic acid (AA), adenosine dyphosphate (ADP), collagen, adrenalin. Concentrations of inductors were chosen according to recommended standards, at that were used least effective concentrations that caused aggregation that increased the sensitivity of the given method in the determination of platelets functional activity.

For the molecular-genetic analysis were used samples of patients’ DNA, extracted from venous blood by the sorbent method. C807T and ITGA2 gene polymorphism was determined by the method of polymerase chain reaction (PCR) using the two-prime system.

Results: The gene interrogation of patients allowed to reveal that in 82,5 % of patients with ACS prevailed ITGA 2 C/T genotype – 40,3 %, Т/Т genotype was revealed in 31,9 % patients. Thus in 72,1 % of patients with an acute disorder of the coronary blood circulation was observed the mutation of ITGA 2 – Т, gene, responsible for platelets adhesion. The study of the aggregation ability in the studied groups allowed to establish, that in patients of all groups the degree of spontaneous aggregation statistically significantly exceeded control limits, at that the most indices were fixed in the group with Т/Т genotype that exceeded control values in 3,02 times. It is worth noting that the carriage of  Т allel was associated with the tendency to the growth of spontaneous aggregation relative to С/С genotype by 34,5 % in С/Т group and reliable increase of spontaneous aggregation in Т/Т genotype group, both relative to С/Т group (by 33 %) and С/С group (by 78,9 %). Analyzing the aggregation ability of platelets with inductors (ADP and AA) the difference in platelets sensitivity was observed only relative to AA-induced aggregation. Thus, in the group of patients with Т/Т genotype the degree of such aggregation exceeded indices of С/С group by 17,3 %, and indices of С/Т group – by 16,5 % (р<0,05 in both cases), at that there was not revealed the essential difference between groups with С/С and С/Т genotype. Analyzing the degree of collagen-induced aggregation in groups it was noticed, that the most indices were fixed in the group with Т/Т genotype – 1,68 times higher than in the control one. T-allel carriage also caused the increase of induced aggregation with collagen relative to С/С genotype by 17 % in С/Т group and reliable increase in Т/Т genotype group, both relative to С/Т (by 43 %) and С/С groups (by 66 %).

Conclusions: ACS syndrome development is associated with the presence of T-allel of ITGA 2 gene, observed in 72,1 % of patients. The presence of Т-allel is combined with the acceleration of platelets spontaneous aggregation, increasing their functional activity in patients with Т/Т genotype 3 times comparing with the control group and by 79 % relative to homozygotes with the “native” С/С genotype. Platelets of patients – carriers of Т/Т genotype had the increased sensitivity to collagen, even under conditions of using low concentrations of an inductor that must be taken into account at personification of the treatment tactics