Saratov JOURNAL of Medical and Scientific Research

Sarattsev A.V.

I.M. Sechenov First Moscow State Medical University Institute of Molecular Medicine, Department of Biomedical Research, Junior Research Assistant, 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
Summary:

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.

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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
Summary:

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.

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