Saratov JOURNAL of Medical and Scientific Research

Bychkov E.N.

SaratovState Medical University n.a. VI. Razumovsky, Department of Psychiatry and Narcology Assistant Professor, Candidate of Medical Science

Association of polymorphism of CYP2D6 and CYP2C9 genes encoding P-450 proteins of cytochrome with arterial hypertension

Year: 2012, volume 8 Issue: №4 Pages: 933-937
Heading: Internal Diseases Article type: Original article
Authors: Borodulin V.B., Shevchenko O.V., Bychkov E.N., Kiselev A.R., Reshetko O.V., Posnenkova O.M., Saratsev A.V., Losev O.E.
Organization: Saratov State Medical University

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.

201204-933-937.pdf913.73 KB

The role of genetic mutations in development of metabolic disturbances in patients with arterial hypertension

Year: 2012, volume 8 Issue: №3 Pages: 751-756
Heading: Internal Diseases Article type: Original article
Authors: Borodulin V.B., Shevchenko O.V., Bychkov E.N., Reshetko O.V., Kiselev A.R., Posnenkova O.M., Zhelezinskaja N.V., Sarattsev A.V., Losev O.E.
Organization: Saratov State Medical University, Saratov Institute of Cardiology, Russia, First Moscow State Medical University n.a. I.M. Sechenov, Clinical Hospital of Ministry of Internal Affairs of the Russian Federation

The article stresses on the study of molecular markers of essential arterial hypertension providing insight into the pathological mechanisms underlying the disease and creation of «genetic passport» for every patient in the future. Objective: To study genetic markers of 5,10-methylenetetrahydrofolate reductase (MTHFR), involved in the metabolism of homocysteine, and N-acetyltransferase 2 (NAT2), ensuring the process of transformation of acetyl-CoAto acetoacetyl-coenzyme A. Methods: The study involved 160 patients with essential hypertension l-lll stages Caucasian (57.5% female.) aged 20-59 years. MTHFR gene polymorphisms and NAT2 in DNA of peripheral blood leukocytes were studied using a set of Wizard Genomic DNA Purification Kit (Promega, USA). Results: It was shown that «slow acetylators» (homozygous for a mutant version of the gene NAT2) were more frequently (p <0.05) determined among patients with hypertension stage 1. It was also revealed the dependence on the presence of hypertension stage mutant allele T (hetero-and homozygous variants) in 677 nucleotide gene MTHFR (r = 0,40, p <0.001). Conclusions: The regularities of the distribution of polymorphic variants of MTHFR and NAT2 gene were found out in hypertensive patients according to the stage of the disease.

201203-751-756.pdf612.78 KB

General methods of identification of narcotic substances in cadaveric urine and biochemical indices in blood at positive identification of drug substances

Year: 2011, volume 7 Issue: №3 Pages: 642-646
Heading: Narcology Article type: Original article
Authors: Bychkov E.N., Serkova S.A., Arsentieva L.A., Frantsuzova T.S., Bluvshtein G.A., Borodulin V.B.
Organization: Saratov State Medical University, Saratov Bureau of Forensic Medical Examination

The goal of the present paper was to find effective biochemical markers of chronic narcotization. Materials and methods. The results of biochemical research of biological liquids in human organism and chromatographic methods of drug substances identification in cadaveric urine were analyzed. Research of 197 samples of different biologic liquids of 10 persons was carried out. Control was fulfilled on the basis of 135 samples of biological liquids took of 12 persons. Methods of identification of drug substances are presented, chromatographic and spectral characteristics of drug substances are described. Interrelations of biochemical indices at positive study of drug substances identification were conducted. The increased urea metabolic concentration in cadaveric blood of drug addicts was revealed in comparison with control specimens. Results. (Numeral results are given in Table 3). Correct correlation of biochemical markers was not established. Conclusion. The present results suppose continued study of informative reliable biochemical markers of chronic drug intoxication

201103_642-646.pdf584.87 KB

Genetic pathogenesis of essential arterial hypertension (the review)

Year: 2011, volume 7 Issue: №1 Pages: 083-087
Heading: Internal Diseases Article type: Review
Authors: Shevchenko O.V., Svistunov А.А., Borodulin V.B., Ruta A.V., Bychkov E.N.
Organization: Saratov State Medical University, First Moscow State Medical University n.a. I.M. Sechenov

It is proved that genetic factors may be considered as fundamental in the development of essential arterial hypertension (AH). Important role in this process belongs to the genes whose products are involved in regulating blood pressure - adrenergic, renin-angiotensin-aldosterone, and homocyclic bradykinin systems. These systems are closely connected by serial and parallel chemical reactions that enable to use genetic testing to determine the state of the whole system. Analysis of polymorphic markers of different groups of genes encoding components of the renin-angiotensin-aldosterone system allows to define the role of each of the pathogenic factor of hypertension in the development of the disease

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