ACADEMIC RESEARCH IN MODERN SCIENCE
International scientific-online conference
8
THE SIGNIFICANCE OF POLYMORPHISMS OF SOME GENES,
RELATED TO PLATELET FUNCTION OF HEMOSTASIS WITH
ANTIPLATELET RESISTANCE
Khodjanova Sh.I.
Alavi A.L.
Tashkent Medical Academy
https://doi.org/10.5281/zenodo.14173047
Relevance.
Platelet activation and aggregation play a key role in the
development of ischemic events. Double antiplatelet therapy with aspirin and
clopidogrel in patients with coronary heart disease significantly reduces the
number of adverse ischemic events. In recent years, much attention has been
paid in the literature to such a concept as resistance to antiplatelet drugs.
According to a number of authors, the range of resistance to aspirin varies
between 5-45%, and to clopidogrel – 4-30%.
The aim
of the work is to determine the frequency and structure of
genetic factors that determine an individual predisposition to the development
of aspirin resistance in patients with coronary heart disease in the Uzbek
population.
Materials and methods:
The study was performed on the basis of the
Department of Cardiology of the RSNPT and MR. The study included 60 Uzbek
patients diagnosed with coronary heart disease (48 men, 12 women; average
age 59.5±8.3 years). The control group consisted of almost 30 healthy persons of
Uzbek nationality, comparable in gender and age with the study group. Genetic
studies were conducted to determine the polymorphism of Leu33Pro of the β3
integrin gene (ITGB3), polymorphism - Thr145Met of the platelet glycoprotein
1b gene, α-subunit (GP1BA), C786T mutation of the nitric oxide synthase 3 gene
(NOS3), platelet ADP receptor mutation (P2RY12, H1/H2); integrin alpha-2 gene
(glycoprotein Platelet Ia/IIa) (ITGA2), C807T mutation.
The results of the study:
In the control group, the frequency of the
mutant allele according to the studied polymorphisms was 16.4% in the ITGB3
gene (Leu33Pro), 164.6% in the CP1BA gene (Thr145Met), 45.3% in the NOS3
gene (C786T), 25.7% in the H1/H2 gene (P2RY12), which is significantly lower
than those frequencies in the study group (32.4%, 43.8%, 61.6% and 38.2%,
respectively, p<0.05). The exception was the C807T (ITGA2) gene, where the
differences with the group of examined patients were insignificant. The analysis
of the frequency of polymorphisms revealed significant frequency exceedances
of mutant ITGB3, CP1BA, NOS3 alleles in homozygous form (OR=1.29; =1.94;
ACADEMIC RESEARCH IN MODERN SCIENCE
International scientific-online conference
9
=2.25, respectively, p<0.001) in patients with antiplatelet resistance. The
frequencies of polymorphisms of the H1/H2 gene differed to a lesser extent
(OR=1.17, p=0.01) and there were no differences in the ITGA2 gene. A significant
dependence of the fibrinogen content in the blood took place only on (and the
GP1BA_Thr145Met genotype (p=0.030).
Conclusions:
The development of antiplatelet resistance in patients with
coronary heart disease in the Uzbek population is associated with the presence
of mutations ITGB3_Leu33Pro, GP1BA_Thr145Met, NOS3_C786T and
P2RY12_H1H2. The greatest differences in the frequency of polymorphisms
were determined for the Thr145Met mutation in the GP1BA gene.
