THE PREVALENCE OF POLYMORPHISMS OF SOME GENESASSOCIATED WITH THE FUNCTION OF PLASMA-PLATELETHEMOSTASIS, WITH ASPIRIN RESISTANCEIN THE KAZAKH POPULATION

Abstract

The relevance of the research topic: Aspirin is the most common antiplatelet drug in world clinical practice. It is a firstline agent in the treatment of acute forms of vascular insufficiency associated with atherosclerosis of the arteries. In addition,
along with antihypercholesterol drugs, aspirin is most often used for primary and secondary prevention of these conditions. A
rather common condition in a population is a decrease in the effectiveness of aspirin, defined by the term «aspirin
resistance». The main cause of aspirin resistance is considered to be the genetic characteristics of patients, whose structure
depends on the specific population.
Objective: To determine the frequency and structure of the genetic factors that determine an individual predisposition to
develop of aspirin resistance, in patients with coronary heart disease in the Kazakh population.
Materials and methods: Design – cross-sectional clinical-genetic study. The study included 98 patients of Kazakh
nationality with a diagnosis of CHD (79 men, 19 women; mean age 58.6±9.7 years). The control group consisted of almost
100 healthy person (the donor) of Kazakh nationality, comparable in sex and age to a study group. Genetic studies were
performed to determine the Leu33Pro polymorphism of the β3 integrin gene (ITGB3), the Thr145Met polymorphism of the
platelet glycoprotein 1b gene, α-subunit (GP1BA), C786T mutation of the gene 3 of nitric oxide synthase (NOS3), m utatsii
platelet ADP-receptor (P2RY12, H1/H2);gene and integrin alpha-2 (platelet glycoprotein Ia/IIa) (ITGA2), mutation C807T
(disruption of protein synthesis).
Statistical analysis. Qualitative data were compared using the χ2 test. The frequency of alleles was estimated by the
method of gene counting, and χ2 was used to detect Hardy-Weinberg deviations from the equilibrium. Polymorphisms
associated with CHD were further analyzed by multidimensional logistic regression.
The results of the study: In the control group, the frequency of the mutant allele for the studied polymorphisms was
14.5% in the ITGB3 (Leu33Pro) gene, 16.5% in the CP1BA (Thr145Met) gene, 41.5% in the NOS3 (C786T) gene, and
H1/H2 (P2RY12) - 27.0%, which is significantly lower than those in the surveyed group (30.1%, 45.9%, 63.8% and 41.3%,
respectively, p<0.05). The exception wasthe C807T gene (ITGA2), where the differences with the group of examined
patients were insignificant.
When analyzing the frequency of polymorphisms, significant frequencies of mutant alleles ITGB3, CP1BA, NOS3 in the
homozygous form (OR=1,37; =1.93; =2.16, respectively, p<0.001) were revealed in patients with aspirin resistance. The
frequencies of the H1/H2 gene polymorphisms differed to a lesser degree (OR = 1.15, p = 0.01) and there were no
differences in the ITGA 2 gene. Wnachimaya dependence in blood fibrinogen occurred only on (and genotype GP1BA_Thr
145 Met (p = 0.040).
Findings:
1. The development of aspirin resistance in IHD patients in the Kazakh population is associated with the presence of
mutations ITGB3_Leu33Pro, GP1BA_Thr145Met, NOS3_C786T and P2RY12_H1H2.
2. The largest differences in the frequency of polymorphisms are determined for the Thr145Met mutation in the GP1BA
gene.
3. There are relationships among the studied polymorphisms of the GP1BA gene not only with aspirin resistance, but
also with an increase in the content of fibrinogen in the blood.