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The contribution of polymorphism С634 П of gene VEGFА in development of cerebral vascular pathology in the patients...
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Khalimova Khanifa Mukhsinovna, Professor of the department neurology of Tashkent medical academy, MD, professor Rakhmatullaeva Gulnora Kutbitdinovna, PhD, Independent competitor of the department neurology
of Tashkent medical academy
Karimov Khamid Yakubovich, Professor of the department neurology of Tashkent medical academy, MD, professor
Boboev Kadir Tuxtabaevich, Professor of the department neurology of Tashkent medical academy, MD, professor E-mail: [email protected]
The contribution of polymorphism 0634 G of gene VEGFА in development of cerebral vascular pathology in the patients with cephalalgic syndrome
Abstract:
Objective. The purpose of research is to study the importance of allele variants of polymorphism C634G of gene VEGF A in the development of the cerebro-vascular pathology.
Materials and methods of research. Materials and methods of research: There were studied 178 patients who form the main group receiving out-patient and stationary treatment in the Republican Clinical Hospital № 1. The control group consisted of 172 conditionally healthy persons of the Uzbek nationality.
Results. during the comparative analysis of frequency of distribution of the alleles and genotypes of polymorphism of gene VEGF A C634G.
Conclusion. Besides the frequency of unfavourable state was defined by homozygotic genotype G/G. Keywords: cerebral vascular pathology, cephalalgic syndrome, polymorphism C634G of gene VEGFA.
The headache being multidisciplinary problem, reduce the quality of life of patients and result in significant burden to the economy of many countries in the world. Many factors have a great importance in the development of headaches, among them the special place is occupied by the pathology of the cerebral vessels. The more researchers have become interested in studying of this pathology over the last time. The molecular-genetic mechanisms of the development of the cerebral vessels underlie this pathology. Thus, one of the factor regulating the processes of the angiogenesis appeared to be vasculoendothelial grows factor (VEGF), which, first of all, has ability to induce angiogenesis and vasculogenesis. VEGF was isolated in 1989 by French doctor N. Ferrara, who was the first taking attention on its contradictory and dual role in the human body [1; 2; 3; 4]. Now it is shown, that VEGF, playing the important role in maintenance of endothelial stability and physiological neoangiogenesis, simultaneously take an active part in processes of neovascularization in the pathological situations, particularly, in the grow of atherosclerotic patch and neoplastic processes at oncogenesis [3; 7; 8; 9; 10]. The further study of VEGF role is considered perspective in relation to development of cardio-vascular diseases in the basis of which the processes of circulation disorders and ischemia lay (ischemic heart disease, disturbances of peripheral blood circulation, disorders of cerebral, retinal blood flow. The main ways of angiogenesis stimulation include stimulation of the proliferation
of endothelial cells; increase in permeability ofvessels and regulation of the production of matrix metalloproteinase [1; 2; 3; 4; 5; 6; 11].
Among several allele variants of this gene the variant VEGFA C634G gains the special importance, because the replacement of nucleotide citozine by guanine in the position 634 occurs if it is available.
The purpose of research is to study the importance of allele variants ofpolymorphism C634G of gene VEGFA in the development of the cerebro-vascular pathology.
Materials and methods of research: There were studied 178 patients who form the main group receiving out-patient and stationary treatment in the Republican Clinical Hospital № 1.
The diagnosis in the patients was made on the basis of clinical-neurologic, neurovisualized examinations: CT of the brain with angiography or MRI of the brain with angioregimen, Molecular-genetic investigation of polymorphism C634G of gene VEGFA (rs 2010963) was also carried out.
The control group consisted of 172 conditionally healthy persons of the Uzbek nationality.
Genom DNA from the samples of peripheral blood (Vacu-tainerBectonDickinsonlnternationalc EDTA) was isolated with use of kits "QIAamp DNA BloodMiniKit", Qiagen (Germany), according to the instruction. Concentration and cleanliness of DNA were estimated on the spectrophotometer NanoDrop 2000
Section 4. Medical science
"ThermoScientific" (USA). Amplification was prformed with the help of thermocycler Amp PCR-system 2720 (AppliedBiosystems, USA) with use of a commercial set of firm ООО NPF Litex (Moscow) accordingly to the instruction of the manufacturer.
Mathematical methods of the analysis.
The frequencies of alleles and genotypes (f) were calculated by standard formula:
f = n/2N and: f = n/N,
where n — prevalence of variant (allele or genotype), N — volume of sample.
The estimation of deviation of distributions of genotypes from initial distribution by Hardi-VainbergХарди-Вайнберга was performed with the help ofthe computer program « GenePop» [12].
The relative deviation of the expected heterozygosis from observed (D) was calculated by formula:
D (hobs hexp)/hexp
where hobs and hexp — observable and expected heterozygosis, respectively.
The estimation of the proportion of rates and 95 % Confidential Interval (OR and CI) was spent with the use a package of the program OpenEpi (ver. 9.3).
Results and discussion
The distribution of genotypes by rs 2010963 in the main and control samples corresponded to expected at balance Hardi-Vain-berg (BHV). In the table 1 the estimation of observable and expected heterogygosis is also presented. As it is visible from the table, in both investigated groups the actual heterozygosis (Hobs) did not prevail expected (H ), and the level of observable heterozygosis was less than expected (D = -0.05 and D = -0.04, respectively).
Table 1. - The level of heterozygosis of polymorphism rs 2010963 of gene VEGFA in main and control groups
Groups Heterozygosis D x2 Р
H exp H'obs
Main group 37.22 34.83 -0.05 0.27 0.4
Control group 22.74 21.51 -0.04 0.114 0.5
In the main group polymorphism rs 2010963 is characterized by relatively high level of theoretically expected heterozygosis (Hexp = 0.37), that is a parameter of average, but close to maximal (0.5), genetic variety in a population at diallele polymorphism. As it is known, by a level of observable heterozygosis it is possible to judge
a measure of genetic variability in a population. In the populational sample the least parameter of observable heterozygosis (Hobs = 0.21) is found out, that testifies to a possible low level of a genetic variety of our population by this locus (about presence ofeffect ofthe founder).
Comparative analysis of frequencies of genotypes and alleles of polymorphism of rs 2010963 of gene VEGFA of the control group with various clinical forms of the cephalalgic syndrome on the background of the pathology of the cerebral vessels allowed identification of a number of associations.
The frequencies of C and G alleles rs 2010963 of gene VEGFA in the main group of the patients accounted 75.3 % and 24.7 %, in the group of control — 62.5 % and 37.5 %, respectively (fig. 1 and tab. 1). The general predisposition to the pathology of cerebral vessels was associated with allele variant G. The relative chance of the development of the cerebro-vascular pathology for carriers of allele G increased reliably 2.2 times in comparison with carriers of the alternative allele C (x 2 = 15.4; P < 0.05; OR = 2.2; 95 %CI 1.47-3.239). Adverse allele G was reliably increased in te main group in comparison with group of control (24 % against 13.1 %) (x2 = 42.2; P < 0.05; OR=4.0; 95 %CI 2.58-6.145).
Then the results of the analysis of association of genotypes rs 2010963 of gene VEGFA with risk of the development of a pathology of the cerebral vessels (fig. 2) are presented.
The comparative analysis of frequencies of genotypes between groups of the patients and control also has revealed statistically significant differences. The frequencies of genotypes C/C, C/G and G/G rs 2010963 of gene VEGFA accounted: 76.2 %, 21.5 % and 2.3 % — in control group, 57.9 %, 34.8 % and 7.3 % — in the main. In the both studied groups the genotype C/C appeared to be the most widespread which was determined with frequency 76.2 % in the united sample of the patients and 57.9 % in sample of the control (X2 = 13.2; P < 0.05; OR = 0.4; 95 %CI 0.27-0.68). The heterozy-gotic genotype C/G was determined 1.9 times more often in group of the patients (34.8 %), than at the control (21.5 %). These differences have achieved a level of the statistical significance (x2 = 7.6; P = 0.001; OR = 1.9; 95 %CI 1.211-3.141). The frequency of unfavourable homozygotic genotype G/G in group of the patients was reliable higher in comparison with the control (7.3 % against 2.3 %). According to culculated coefficient of the ratio of chances, the risk of development ofpathology of the vessels in the carriers of this genotype is higher 3,3 times reliably, than in carriers of other genotypes (X2 = 4.7; P = 0.03; OR=3.3; 95 %CI 1.05-10.36).
allele C allele G
Fig. 1. Frequency of distributions of alleles of gene C VEGFA G 634
Indicators correlation among ferrokinetic performance, copper content in blood serum ceruloplasmin women with.
Fig. 2. Frequency of distributions of genotypes of gene C VEGFA G 634
Thus, during the comparative analysis of frequency of distribution of the alleles and genotypes of polymorphism of gene VEGFA C634G, between main and control groups the statistically reliable differences have been revealed. Thus the general predisposition to a pathology of cerebral vessels was associated with allele variant G. In the carriers of allele G the relative chance of development of a pathology of cerebral vessels was reliably increased in
more than in 2 times in comparison with carriers of alternative allele C. Besides the frequency of unfavourable state was defined by homozygotic genotype G/G, which was higher in group of the patients in comparison with the control (7.3 % against 2.3 %). So, the ratio of chances of the risk of development of pathology of the cerebral vessels in the carriers of this genotype was reliably high more than in 3 times, than in carriers of other genotypes.
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Hamdamova Muhayo Tuhtasinovna, Bukhara state medical institute, Uzbekistan E-mail: [email protected]
Indicators correlation among ferrokinetic performance, copper content in blood serum ceruloplasmin women with extended wear intrauterine device
Abstract: The aim was to evaluate the correlations between ferrokinetic indicators, copper and ceruloplasmin in serum of women with prolonged wearing intrauterine device (IUD). There was an inverse correlation relationship between transferrin and serum ferritin in women with IUDs, which increases with increasing duration of wearing the Navy. Within 12 months of the
