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Pharmacogenetics and Pharmacogenomics

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No 2 (2016)
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FROM EDITOR

CURRENT REVIEW

4-11 2646
Abstract
Isozymes of cytochrome P450 enzymes are major catalyzing phase I biotransformation drugs that usually leads to the formation of hydrophilic and little active metabolites. The greatest role drugs play biotransformation CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of cytochrome P450 under the influence of drugs is an important and clinically relevant mechanism pharmacokinetics drug interactions. Study of the activity of isoenzymes of cytochrome P450 using phenotyping methods (determination of the concentration of specific substrates and metabolites thereof biological fluids) against application of drugs to predict adverse drug reactions resulting from drug-drug interactions. Promising for clinical practice is the use of phenotyping for the cytochrome P450 is not exogenous and endogenous substances (eg the ratio of cortisol / 6-beta-hydroxycortisol in urine to evaluate the activity of CYP3A4), which is the most safe and minimally invasive approach to research participants.

PHARMACOGENETICS STUDY

12-18 605
Abstract
Introduction. The efficiency and safety of a drug therapy depends on the peculiarities of functioning of P450 cytochrome group and transporting proteins a lot. Materials and methods. We have studied the peculiarities of some P450 cytochrome polymorphisms’, SLCO1B1 transporting proteins’ and P-glycoproteins carriage of the healthy volunteers in Nanai ethnic group, living in Russia and compared them to the carriage of SNP in Russian population according to the literary data. Results. After performing the real-time polymerase chain reaction on the samples of 70 healthy volunteers from Nanai ethnic group for the CYP2C9*2 (C430T) polymorphism we have determined 70 CC-genotype carriers, for the CYP2C9*3 (А1075С) polymorphism – 62 AA-genotype carriers, AC-genotype – 8 carriers. For the CYP2C19*2 (G681A) polymorphism we have determined 39 GG-genotype carriers, GA-genotype – 28 carriers, for the CYP2C19*3 (G636A) polymorphism – 58 GG-genotype carriers, GA-genotype – 12 carriers, for the CYP2C19*17 (C806T) polymorphism – CC-genotype – 67 carriers, CT-genotype – 3 carriers. For the CYP2D6*4 (G1846A) polymorphism – GG-genotype – 68 carriers, GA-genotype – 2 carriers. For the ABCB1 (C3435T) polymorphism – CC-genotype – 19 carriers, CT-genotype – 39 carriers. For the SLCO1B1*5 (T521C) polymorphism – TT-genotype – 41 carrier, CT-genotype – 25 carriers. The distribution of the genotypes fitted the Hardy-Weinberg equilibrium for all the polymorphisms except the CYP2C9*2. There were also significant differences in allele frequencies for some polymorphisms between the Nanai’s and the Russians. Conclusions. In Nanai population there are polymorphisms, connected with the decrease of safety and efficiency of drug therapy. Studying the ethnic differences might influence the determination of the priority in the introduction of the pharmacogenetic test in clinical practice in different regions of Russia.

CLINICAL STUDY

19-23 426
Abstract
Actuality. Cytochrome P450 enzymes activity tends to decrease with age, which is the reason why drugs’ metabolizing is slowed down. Such changes lead to a larger number of adverse side effects. This research is dedicated to evaluating activity changes of CYP2C9 isoform, which is involved in metabolism of a lot of significant drugs. Objective. The purpose of this research is to compare CYP2C9 isoform activity in elderly patients with that in people of the first period of middle age. Materials and methods. The work was carried out in 2 phases. The first phase evaluated the activity of cytochrome CYP2C9 in elderly and geriartric patients. The study included 18 elderly and senile patients, mean age 71,6 ± 9,6 years. In the second phase we evaluated the efficacy and safety of losartan trials in 18 healthy volunteers of the first period of mature age, mean age 26,3 ± 3,5 years. E-3174 (losartan’s metabolite) / losartan concentration in the urine ratio was used to evaluate CYP2C9 isoform activity. Results and discussion. According to the study the E-3174/losartan concentration ratio in elderly patients was 1,84 ± 0,15. In healthy young volunteers the E-3174/losartan ratio was 3,28 ± 0,77. In young patients the E-3174/ losartan ratio, the concentration of E-3174 and losartan concentration were higher than in elderly and senile patients, which indicates that the CYP2C9 activity in that group is lower than that in young volunteers of the first period of middle age. Conclusion. The activity of CYP2C9 in elderly people has a tendency to decrease.

PERSPECTIVE ON PHARMACOGENETICS AND PHARMACOGENOMICS

24-26 572
Abstract
In contemporary guidelines on the management of patients with acute coronary syndrome (ACS) an important place is given dual antiplatelet therapy. The relatively high frequency of complications and recurrences in such patients indicates the imperfections of modern approaches for antiplatelet therapy. The results of contemporary research showed a significant effect of the personalization of dual antiplatelet therapy with clopidogrel on outcomes and course of the ACS, because the influence of genetic factors on its antiplatelet effect is significantly. Drug of the third generation thienopyridines ticagrelor is not a prodrug like clopidogrel, however, its efficiency and safety is affected by many factors. This article describes current research in sphere of personalization of dual antiplatelet therapy of ACS on the basis of pharmacogenetics and discusses the potential of research the clinical pharmacogenetics of ticagrelor as a component of the personalization of dual antiplatelet therapy in patients with ACS.
27-31 383
Abstract
The prevalence of atherosclerosis of the arteries of the lower extremities in the population is a socially significant problem in connection with high frequency of major amputation, disability and mortality in this group of patients. Diabetes 2 type along with smoking and arterial hypertension is a famous risk factor for peripheral atherosclerosis (in the limit of macrovascular complications). In Russian and foreign literature describes the clinical features, conventional methods of diagnosis and treatment of patients with obliterating atherosclerosis on the background of diabetes type 2. However, despite knowledge of the issue and the use of modern methods of diagnosis and treatment, the prognosis of the disease remains a serious, and level of cardiovascular death in this cohort is 6 times higher than the main population. In this regard, a perspective direction of the world and Russian scientists is to develop a method of pharmacogenetic testing as a instrument for personalized therapy of comorbid patients with peripheral atherosclerosis.

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ISSN 2588-0527 (Print)
ISSN 2686-8849 (Online)