CYP2C19 is known to be the main enzyme of biotransformation of proton pump inhibitors (PPIs), whereas the CYP2C19 gene is highly polymorphic. Genotyping and phenotyping together represent more reliable data about patient’s CYP2C19 activity. Purpose The aim of the study was to investigate the applicability of urine metabolic ratio of omeprazole for CYP2C19 phenotyping in Russian peptic ulcer patients with different CYP2C19 genotypes. Patients and methods A total of 59 patients (19 men and 40 women) aged 18–91 years (mean age 53.5±15.1 years) from four Moscow clinics who were diagnosed with an endoscopically and histologically proven peptic ulcer or had a history of endoscopically and histologically proven ulcers in the past were recruited. Peripheral venous blood (6 mL) was collected for DNA extraction, and real-time polymerase chain reaction was performed for the analysis of CYP2C19*2G681A (rs4244285), CYP2C19*3G636A (rs4986893) and CYP2C19*17C-806T (rs12248560) polymorphisms. Urine samples of patients were collected in the morning between 6 am and 9 am, before food or drug intake, after at least 3 days of twice daily (b.i.d.) omeprazole intake. Omeprazole and 5-hydroxyomeprazole concentrations in the urine were measured using high-performance liquid chromatography with mass spectrometry. Results Of the 59 patients, there were 27 (45.8%) extensive metabolizers (EMs; CYP2C19*1/*1), 16 (27.1%) ultrarapid metabolizers (UMs; CYP2C19*1/*17, CYP2C19*17/*17), 14 (23.7%) intermediate metabolizers (IMs; CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*3/*17) and two (3.4%) poor metabolizers (PMs; CYP2C19*2/*2). Median metabolic ratio (25%–75% percentiles) were 1.03 (0.69–1.36) for EMs, 1.95 (1.33–2.68) for UMs, 1.40 (0.78–2.13) for IMs+PMs and 1.26 (0.82–1.99) for the whole sample. A statistically significant difference in metabolic ratio (Mann–Whitney U test) was found between UMs and EMs (p=0.001) and in the multiple comparison Kruskal–Wallis test (p=0.005). Conclusion We found a connection between particular CYP2C19 genotypes and urine metabolic ratio of omeprazole in Russian peptic ulcer patients. This method needs to be improved as in our modification it worked mainly for UMs and did not differentiate all patients according to omeprazole biotransformation activity.

To identify the association between the 5-HTTLPR polymorphism of the serotonin transporter gene with the efficacy and tolerability of antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI). Materials and methods. A complex clinical-psychopathological and genetic study of 38 patients with depression during SSRI treatment was conducted. Results and conclusions. Statistical associations between the 5-HTTLPR polymorphism and the levels of remission and tolerability were identified: carriers of the SS genotype rarely achieved remission and developed more severe side effects.

Gene polymorphisms of cytochrome P-450 CYP2 encoding proteins of cytochrome P-450 are essential forantihy-pertensive drugs metabolism. Purpose: We study the associations of functionally defective allele variants of CYP2D6 gene and CYP2C9 gene with the degree of arterial hypertension (AH). Materials and methods: Samples of DNA of leukocytes of blood of 150 patients with AH without the associated clinical conditions (56% of women) at the age of 20-59 years have been investigated. For the study of polymorphism of genes the pharmacogenetic biochip developed in the Institute of Molecular Biology n.a. V. A. Engelgardt has been used. Comparison of frequencies of occurrence of signs has been carried out on the basis of chi-square criterion. Results: It has been revealed that homozygotes by mutant A1075C, C430T alleles of CYP2C9gene and G1934A of CYP2D6 gene have been significantly more common among patients with hypertension III (p=0.01). Conclusion: The research works on genes of system of P-450 cytochrome have important clinical value for rationalization of pharmacotherapy of hypertension. The increased frequency of occurrence of mutant allele of CYP2D6 and CYP2C9 genes in patients with hypertension III requires special attention to the problem of efficiency and safety of application of hypotensive drugs for the patients.
Saratov Journal of Medical Scientific Research. 2012. Vol. 8, № 4. P. 933–937.

Gene polymorphisms of cytochrome P-450 CYP2 encoding proteins of cytochrome P-450 are essential forantihy-pertensive drugs metabolism. Purpose: We study the associations of functionally defective allele variants of CYP2D6 gene and CYP2C9 gene with the degree of arterial hypertension (AH). Materials and methods: Samples of DNA of leukocytes of blood of 150 patients with AH without the associated clinical conditions (56% of women) at the age of 20-59 years have been investigated. For the study of polymorphism of genes the pharmacogenetic biochip developed in the Institute of Molecular Biology n.a. V. A. Engelgardt has been used. Comparison of frequencies of occurrence of signs has been carried out on the basis of chi-square criterion. Results: It has been revealed that homozygotes by mutant A1075C, C430T alleles of CYP2C9gene and G1934A of CYP2D6 gene have been significantly more common among patients with hypertension III (p=0.01). Conclusion: The research works on genes of system of P-450 cytochrome have important clinical value for rationalization of pharmacotherapy of hypertension. The increased frequency of occurrence of mutant allele of CYP2D6 and CYP2C9 genes in patients with hypertension III requires special attention to the problem of efficiency and safety of application of hypotensive drugs for the patients.
Borodulin V.B., Shevchenko O.V., Bychkov E.N., Kiselev A.R., Reshetko O.V., Posnenkova O.M., Saratsev A.V., Losev O.E. Association of polymorphism of CYP2D6 and CYP2C9 genes encoding P-450 proteins of cytochrome with arterial hypertension // Saratov Journal of Medical Scientific Research, Vol. 8, Issue 4, 2012, pp. 933-937

At present it is obvious that genetic peculiarities of patients are the major reason for individual differences in pharmacological responses to (β-adrenoblockers. Furthermore ADRB1 gene polymorphism is responsible for the efficiency of (β-adrenoblockers. Thus, a real prospect exists for an individualized approach to administration of (β-adrenoblockers and selection of dosage based on patient’s genotype, which must undoubtedly increase efficiency of the administered therapy. Reviewfocuses on gene polymorphism responsible for (β-adrenoblockers pharmacodynamics and on the clinical significance of the polymorphism detection to individualize drug therapy based on patient’s genotype.
A.N. Levanov, I.V. Ignatyev, D.A. Sychev, S.I. Bogoslovskaya, A.A. Svistunov BETA-ADRENORECEPTORS GENETIC POLYMORPHISM CONNECTION WITH BETA-BLOKER THERAPY EFFICACY IN PATIENTS WITH CARDIOVASCULAR DISORDERS // Saratov Journal of Medical Scientific Research, Vol. 5, Issue 1, 2009, pp. 41-44