Presented a review of pharmacogenetic markers CYP3A5 and P-glycoprotein and it's role in increasing blood pressure and development of hypertension. Expression of the CYP3A5 isoform in the kidney is involved in the regulation of activity RAAS, aldosterone and sodium reabsorption. An additional value in the regulation of aldosterone activity of the genetic polymorphism of the known efflux- transporter of the P-glycoprotein is shown, which can also increase the level of blood pressure. Calcium antagonists and amlodipine are substrates for CYP3A5. Several foreign and domestic clinical research have shown the effect of the expression of the CYP3A5*1 allele and the variant 3435T allele of the ABCB1 gene in the more powerful hypotensive effect of amlodipine and development of vasodilatation side effects. With high expression of CYP3A5*1 the hypotensive effect of amlodipine is higher and accompanied by vasodilatation side effects.

In review accumulated present scientific information about the value and principles of action of main oral hypoglycemic drugs in treatment of diabetes mellitus (DM), and the role of polymorphic variants in the genes KCNJ11, ABCC8 and TCF7L2, recognized source responsible for the predisposition to the DM, individual response to treatment with oral hypoglycemic agents. Reviewed the functions of proteins encoded by these genes, main polymorphic variants, indicated directions for further scientific research.

Today it is known that the second-generation Hl-antihistamines are substrates for the P-glycoprotein, that is encoded by the multiple drug resistance gene. The metabolism of the second-generation Hl-antihistamines involves a number of cytochrome P450 isoenzymes that encoded by the corresponding genes. All these noted genes are polymorphic, that can affect the activity of encoded proteins. Efflux alteration of second-generation Hl-antihistamines, as well as modifications in their biotransformation, can affect their efficacy and safety. The purpose of this review was to generalize current available information about pharmacogenetic characteristics of second-generation Hl-antihistamines and to suspect interindividual variability mechanisms of their efficacy and safety for allergic diseases.

According to the literature, a decrease in vitamin D in the blood is associated with various diseases in children, such as rickets, osteoporosis, juvenile idiopathic arthritis, cardiovascular, oncological and allergic diseases, diabetes. Associations of gene mutations of the vitamin D system with the above diseases have been found. This article examines the metabolism of vitamin D, significant genes that play an important role in the metabolism of vitamin D and single nucleotide substitutions in them, associated with a reduced concentration of vitamin D in the blood and various diseases. Also, modern recommendations on nutrition and drug treatment of hypovitaminosis in childhood are considered.

Purpose. The purpose of this study was to examine frequency of genetic polymorphism of CYP3A5*3 (rs776746 A>T in women with non-developing pregnancy. Methodology. The study included all women admitted to the Department of obstetrics and gynecology of the Peter Great clinic with a verified diagnosis of non-developing pregnancy. In parallel, the control group included women with normal pregnancy, comparable in age and the presence or absence of comorbidities. After obtaining consent from women, peripheral venous blood was collected for genetic research. Gen CYP3A5*3/*1 (6986A>G) polymorphism was determined by real-time polymerase chain reaction method using the developed sets («Synthol», Russia). Comparison of the detected allele frequencies was performed using Chi-square method. The Graphpad Prism 5.0 statistical program was used. Results. 53 persons were included in the study group of women with non-developing pregnancy. The control group, comparable in age and comorbidity, included 92 people. The frequency of minor allele Т in the study group was 8 %, in the control group - 4 % (p = 0.1; 2). The distribution of genotypes in the main group was as follows: ТТ - 0.02; TC - 0.13; CC - 0.85. The distribution of genotypes in the control group: ТТ - 0.01; TC - 0.05; CC to 0.94. The distributions corresponded to the Hardy-Weinberg equation. Conclusion. The results of the study indicate a tendency to a higher frequency of minor allele Т in the group of women with non-developing pregnancy compared to women whose pregnancy was normal at the time of the study. The obtained data may indicate a possible role of CYP3A5 activity in the pathogenesis of non-developing pregnancy, or in the effectiveness of drug therapy, since this enzyme performs the function of endogenous metabolism of a number of sex hormones (progesterone, testosterone).

Introduction. The efficacy of pharmacological treatment of arterial hypertension depends of many factors. Some of them are polymorphisms of ABCB1 and CYP3A genes which take part in drug metabolism. The aim of present study was to determine the influence of ABCB1 (rs4148738) and CYP3A4*22 (rs35599367) polymorphisms on the efficacy and safety of antihypertensive therapy with amlodipine. Methods. The study included 100 patients diagnosed with essential arterial hypertension (I-II stages) who received amlodipine, 53 of them are men and 47 are women (mean age 60.15 ± 10.31 years). Genotyping of ABCB1 (rs4148738) and CYP3A4*22 (rs35599367) polymorphisms was performed by reaL-time polymerase chain reaction. To evaluate the efficacy of antihypertensive therapy an office bLood pressure measurement was used before and after 12-week treatment with amlodipine. The safety of treatment was estimated by physical examination. Results. During the research of ABCB1 (rs4148738) polymorphism 19 patients with the CC genotype, 49 patients with the CT genotype and 32 with the TT genotype were identified. The distribution obeys the Hardy-Weinberg Law (х² = 0.001; p = 0.97) which indicates that the sample is representative. Comparison of the three groups of patients by ABCB1 polymorphism revealed significant differences in the frequency of adverse drug reactions caused by amlodipine treatment (Pearson’s chi-squared test, p = 0.02). The greatest number of them was observed in patients with the TT genotype, the minimal - in patients with the CC genotype. There were no statistically significant differences in the change of systolic (SBP) and diastolic (DBP) blood pressure between the three groups (Kruskal-Wallis test, p = 0.41 and p = 0.08 respectively). However when comparing patient groups carriers of at least one T-allele and non-carriers of this allele (CT + TT and CC) greater DBP reducing was found in patients with CC genotype (Mann-Whitney U test, p = 0.025). For the CYP3A4*22 (rs35599367) polymorphism the distribution was: 98 patients with CC genotype and 2 heterozygotes CT. Due to low genotype frequency of CT genotype it was impossible to estimate the role of this polymorphism in treatment with amlodipine. Conclusions. Based on the results obtained it can be concluded that lower efficacy of amlodipine in reducing DBP was performed in patients who are carriers of at least one T-allele. The genotype TT is most associated with the emergence of adverse effects while in patients with the CC genotype their frequency is minimal and for the CT genotype it is at an intermediate level.

This article highlights modern approaches in the diagnosis and treatment of critical patients in terms of personalized medicine. Biomarkers of such conditions as acute renaL failure, acute respiratory distress syndrome, sepsis are described. The roLe of pharmacokinetics and pharmacogenomics in the intensive care unit is reported.

The problem of translation of modern achievements of personalized medicine into everyday clinical practice is actively discussed, but far from being resolved. The authors presented the clinical case of adverse course of juvenile myoclonic epilepsy in a 63-year-old woman. The authors emphasized that after the correction of antiepileptic therapy, taking into account the position of personalized medicine, not only achieved pharmacoinduced remission of epileptic seizures, but also significantly improved the quality of life of the patient.