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MOLECULAR-GENETIC FEATURES OF VASCULAR THROMBOSIS
Musashaykhov U. Kh.
Andijan State Medical Institute.
Annotation.
During the study, in 107 patients with vascular thrombosis of various
localization, the associative relationship of Leu33Pro in the integrin beta-3 (ITGB3) gene in
the formation of pathology data was analyzed. In the studied groups, the actual distribution
of C807T polymorphism genotypes corresponded to those expected at the Hardy-Weinberg
equilibrium (p<0.05).
Key words:
ischemic stroke, myocardial infarction, deep vein thrombosis of the lower
extremities, genetic polymorphism Leu33Pro ITGB3.
Relevance.
In recent years, there has been an increase in the proportion of vascular
thrombosis of various localizations among young people [4]. The incidence, according to
various sources, varies from 3 to 23 per 100,000 people [2]. Hereditary thrombophilia can
most often be considered as a provocateur in these situations, since some patients have
occlusion of the cerebral and coronary arteries due to intravascular thrombosis during
examination [1, 6]. Thrombophilia is defined as a violation of hemostasis and hemorheology,
characterized by an increased tendency to develop thrombosis or intravascular coagulation,
which is based on acquired and genetically modified blood clots. conditioned disorders in
various parts of hemostasis and hemorheology [3]. Among the factors that increase the risk
of thrombosis, platelet receptor genes are very important. In this case, a genetic marker of
the platelet receptor gene for collagen (ITGA2 807C>T) and fibrinogen (ITGB31565T>C) is
analyzed. With a defect in the collagen receptor gene, platelet adhesion to the vascular
endothelium and to each other increases, which leads to increased thrombosis. When
analyzing the genetic marker ITGB31565T>C, it is possible to identify the effectiveness or
ineffectiveness of antiplatelet therapy with aspirin. Disorders caused by mutations in these
genes increase the risk of thrombosis, myocardial infarction, and ischemic stroke [5].
Material and methods of research.
During the genetic study, we examined 107 patients
with vascular thrombosis of various localizations who were in the neurological,
cardiological and surgical departments of the clinic of the Andijan State Medical Institute
and the Andijan branch of the Republican Scientific Center for Emergency Medical Care,
who formed the main group. Among them, patients with DVT n=35, with IS n=35, with MI
n=37. The control group consisted of 103 conditionally "healthy" individuals without
thromboembolic diseases (TES) at the moment and in the anamnesis. Diagnosis of these
diseases was carried out in accordance with currently accepted clinical recommendations.
Isolation of a DNA molecule from peripheral blood was performed using the Ampli Prime
RIBO_prep kit.
Genotyping of the Leu33Pro ITGB3 polymorphism was performed using
the Tag Man probe method on a Rotor-Gene Q amplifier (Quagen, Germany), using a
commercial test kit of Litech LLC (Russia).
Statistical processing of the results was performed using the standard OpenEpi V.9. 2
application software package. The deviation of the empirical genotype frequencies from the
theoretically expected Hardy–Weinberg distribution was analyzed using the Statistica 6.0
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software package. The frequencies of both alleles and Leu33Pro genotypes in the integrin
beta-3 (ITGB33
)
gene are presented as absolute values. numbers and
percentages. Accordingly, differences between groups were evaluated using the χ
2 criterion
.
Moreover, to quantify the effect of each variant on disease risk, univariate odds ratios (OR)
were calculated with corresponding 95% confidence intervals (95% CI).
The aim
of the study is
to study the frequency of distribution and evaluate the relationship
of the Leu33Pro polymorphism in the integrin beta-3 (ITGB3)
gene in patients with vascular
thrombosis of various localizations.
Results obtained and their discussion
In the study, the proportion of Leu and Pro alleles in patients with vascular thrombosis of
various locations and in the control group Leu и Prowas 91.1% and 8.9% versus 95.6% and
4.4%, respectively. Statistical processing revealed a slight decrease in the frequency of the
wild Leu allele (χ
2
=3.4; P=0.06; OR=0.5; 95%CI:0.21-1.06) and a tendency to increase the
mutant Pro allele was found in patients with vascular thrombosis of various localizations
compared to conditionally healthy donors. The calculated coefficient of the odds ratio
showed that the chance of detecting a functional unfavorable Pro allele in the respondents of
the main group increased 2.1 times compared to the representatives of the control group
(χ
2
=3.4; P=0.06; OR=2.1; 95%CI:0.94-4.83).
As can be seen (Table 1), the frequency of the unfavorable Pro/Pro genotype among patients
with vascular thrombosis of various localizations was slightly higherthan in the control
group (0.9% vs. 0.0%, respectively, with χ
2
=1.0; P=0.3).
Table-1.
Association between the Leu33Pro polymorphism in the integrin beta-3 (ITGB3) gene
in patient and control groups
Study groups
Alleles
and
genotypes
Statistical difference in relation to the control group
Odds ratio
χ2
p-value
OR
95% CI:
Main group
(n=107)
Leu
0.5
0.21 – 1.06
3.4
0.06
Pro
2.1
0.94 – 4.83
Leu/Leu
0.5
0.20 – 1.11
3.1
0.08
Leu/Pro
2.0
0.85 – 4.71
2.6
0.1
Pro/Pro
***
***
1.0
0.3
Also, the wild Leu/Leu genotype of the study group was found to be slightly lower
compared to the control group (χ
2
=3.1; P=0.08; OR=0.5; 95%CI:0.20–1.11). This means that
there is no association of these genotypes (Leu/Leu, Pro/Pro) with respect to the formation
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of vascular thrombosis of various localizations, such as DVT, AI, MI. However, there is a
tendency to increase the proportion of carriers of the unfavorable Leu/Pro genotype among
patients compared to the control group (15.9% vs. 8.7%, respectively).. 1). According to the
odds ratio, the risk of developing vascular thrombosis of various localizations in the
presence of this genotype increases 2.0 times (χ
2
=2.6; P=0.1; OR=2.0; 95%CI:0.85-4.71).
(Table 1).
Conclusion.
Thus, the analyzed data of the study showed that, in patients with DVTNA, IS,
and MI, the detection of the minor Pro allele and the associated unfavorable Leu/Pro
genotype was associated with a low risk of developing and relapsing thrombogenic
complications as a result of a moderate increase in platelet aggregation ability. Also, if the
Pro /Pro mutant genotype was detectedPro in the main group, there was no risk of
developing these pathologies.
List of literature.
1.
Kapustin S. I., Shmeleva V. M., Sidorova Zh. Y. and others. Molecular determinants
of hereditary thrombophilia: current state and prospects of gene diagnostics (literature
review). Bulletin of Hematology. 2011;VII(4):84–90.
2.
Chiasakul T, De Jesus E, Tong J, Chen Y, Crowther M, Garcia D, Chai-Adisaksopha
C, Messé SR, Cuker A. Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A
Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019 Oct;8(19):e012877.
3.
Dautaj A, Krasi G, Bushati V, Precone V, Gheza M, Fioretti F, Sartori M, Costantini
A, Benedetti S, Bertelli M. Hereditary thrombophilia. Acta Biomed. 2019 Sep 30;90(10-
S):44-46. doi: 10.23750/abm.v90i10-S.8758.
4. Hathidara MY, Saini V, Malik AM. Stroke in the Young: a Global Update. Curr Neurol
Neurosci Rep. 2019 Nov 25;19(11):91.
5. Liu H, Wang Y, Zheng J, Li G, Chen T, Lei J, Mao Y, Wang J, Liu W, Zhao G, Tacey M,
Yan B. Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are
associated with increased ischemic stroke risk: Evidence from a comprehensive meta-
analysis. Int J Stroke. 2017 Jan;12(1):46-70.
6. Salehi Omran S, Hartman A, Zakai NA, Navi BB. Thrombophilia Testing After Ischemic
Stroke: Why, When, and What? Stroke. 2021 May;52(5):1874-1884. doi:
10.1161/STROKEAHA.120.032360. Epub 2021 Apr 20.
