Isolation genomically second DNA from the venous blood of the patients was conducted meto- house fenolhloroformnoy extraction. Amplification of polymorphic sections was carried out using a polymerase chain reaction on an RNS-2 thermal cycler (manufactured by Techne, United Kingdom). Amplification was carried out in a reaction mixture of the following composition: 67 mmol Tris-HCl (pH 8.8), 16.6 mmol ammonium sulfate, 0.01% Tween-20, 0.5-1 M Mg Cl, 2.02 mM dNTP 33 nanograms of each primer and 1.5 units. DNA polymerase tag. PCR products were analyzed by electrophoresis in a 1.5% agarose gel with the presence of ethidium bromide.
A group of patients with type 2 diabetes mellitus was also formed, who did not experience hypertension, which numbered 80 people.
The results of the research are presented in the tables and histograms.
Thus, the data obtained indicate the presence of significant differences in the frequencies of alleles of the studied genes, which indicates their connection with the development of hypertension. Allele I and the genotype I / I of the ACE gene reduce the risk of developing hypertension, and allele D, on the contrary, increases the risk of its development. At the same time, the protective effect of genotype I / I is more pronounced than that which presupposes D / D homozygotes. The markers of high risk of hypertension are the allele M and especially the M / M genotype of the AGT gene, while the T allele protects it from early developmental pathology. The predisposing effect of the M / M genotype of the AGT gene is more pronounced than the protective effect of the T / T variant. The carrier of the allele A and the genotype A / A of the AT2R1 gene is linked to a reduced one, and the allele CC, on the contrary, is associated with an increased risk of hypertension. At the same time, the protective action of A / A homozygotes is manifested to a greater extent than the predisposing effect of the C / C genotype.
The analysis of the data presented in relation to the polymorphism of the chymase gene does not find a reliable correlation at the moment, however, this trend requires further study on a larger number of the examined patients.
We also studied for the first time the polymorphism of the ACE gene in patients with type 2 diabetes mellitus in combination with hypertension and the evaluation of the effectiveness of drug therapy with ACE inhibitors.
Under supervision there were 135 people. The average age was 61.6 years. The average duration of diabetes was 7.1 years. All patients were treated with hypoglycemic drugs, the dose of which during the observation did not change. The average level of blood pressure was 171.2 + 2.9 / 104.6 + 1.4 mm Hg. Art. According to the severity of hypertension (mild, moderate and severe), 3 groups of patients were formed (2 groups of 30 people each and one group of 45 people) who received treatment with various drugs from the group of ACE inhibitors. A group of patients who did not respond to treatment with ACE inhibitors comprised a control group of 30 people.
General clinical studies were carried out, Hb A 1c, total cholesterol, triglycerides, LDL and HDL were determined. Along with the traditional clinical and instrumental study, the ACE gene was typed in accordance with the method described above.
In all patients, treatment with drugs of the ACE inhibitor group (enalapril, perindopril, cilazapril) was used in the average therapeutic dose. Monotherapy with these drugs was carried out in patients whose degree of arterial hypertension was assessed as mild and moderate. Patients with severe arterial hypertension were excluded from the examination because they needed combined antihypertensive therapy. Contraindications to the inclusion of patients in the study were also marked decompensation of carbohydrate metabolism, severe competing diseases (heart failure, marked atherosclerosis of cerebral vessels, chronic renal failure, and severe liver disease).
The effectiveness of the therapy was assessed by us according to the following criteria: excellent – a decrease in diastolic pressure below 90 mm Hg. Art., good – reduction of diastolic pressure by more than 10% compared to baseline, satisfactory – reduction of diastolic pressure by less than 10% compared to baseline.
Dose adjustment of the drug was carried out, if necessary, after 2 weeks of therapy. The lack of a satisfactory effect served as the reason for the transfer of patients to the group who did not respond to the treatment, and they were prescribed therapy with б -blockers or calcium antagonists in combination with diuretics.
Thus, a group of patients suffering from arterial hypertension and type 2 diabetes mellitus resistant to treatment with ACE inhibitors, meeting all the requirements of representativeness by age and sex criteria, was formed.
The study showed good tolerability. In none of the observed cases, the occurrence of side effects requiring discontinuation of the drug was recorded. An excellent result was observed in 42 patients treated with cilazapril, 11 patients receiving perindopril, and 1 patient receiving enalapril. A good result is in 3 patients who received cilazapril, 18 patients who received perindopril, and 11 patients who received enalapril. A satisfactory effect was observed in 1 patient on perindopril and 18 patients who received enalapril. The highest efficacy of antihypertensive therapy was observed in the group of patients receiving cilazapril.
In groups of patients for whom therapy with ACE inhibitors was effective (tab. 23), genotypes I / D and D / D prevailed, whereas in the group of patients for whom this therapy was ineffective, genotype I prevailed. I. This can be explained by the fact that the genotype I / I ACE gene is characterized by relatively low ACE activity in plasma, while the D / D genotype, by contrast, is characterized by high enzyme activity in tissues and blood. It can be assumed that the development of arterial hypertension in patients with genotype I / I is determined, apparently, by other factors of pathogenesis, which makes them insensitive to treatment with ACE inhibitors.
Thus, the results of our study can be used in the selection of a drug for the treatment of arterial hypertension, taking into account the genotyping of patients.
At the moment, it is obvious that drugs of the ACE inhibitor group are the drugs of choice in the treatment of arterial hypertension in diabetic patients, since they do not have a negative effect on the functional activity of vital systems and at the same time have a number of favorable therapeutic effects. Drugs of this class do not adversely affect the state of the central and autonomic nervous systems, which allows maintaining a good quality of life, increasing tolerance to physical exertion. ACE inhibitors are metabolically neutral drugs: against the background of their use, there are no changes in the lipid profile, changes in the uric acid level, blood glucose level and insulin resistance. The absence of changes in the biochemical blood test was confirmed in our study.
Moreover, the beneficial effect of ACE inhibitors on some homeostasis indicators was noted: a decrease in the level of the plasminogen tissue activator inhibitor, an increase in the level of the plasminogen tissue activator.