Abstract
Drug therapeutic efficiency and development of unfavorable pharmacologic responses as well as the disease predisposition are caused first of all by patient’s genetic features. Genetic variations in genes encoding drug-metabolizing enzymes and transporter proteins are essential to understand the ethnic differences in disease occurrence, development, prognosis, therapeutic response and toxicity of drugs. For that reason, it is necessary to establish the normative frequency distribution of genotypes and alleles of these genes in a particular population. Data on frequency of pharmacogenetic polymorphisms in the of Belarus population are limited. The goal of our investigation was to analyze the frequency distribution of genotypes and alleles of genes encoding drug-metabolizing enzymes (CYP1А2, CYP2D6 – I phase; GSTs, NAT2 – II phase) and transporter protein MDR1 in the population of Belarus and comparisons with other ethnic populations. Our results indicate that clinically important genes are genetically highly variable and differ considerably between populations. Differences in allele frequencies across continents should be considered when designing clinical trials of new drugs continents should be considered when designing clinical trials of new drugs.
Highlights
One of the important problems of drug therapy is variability of patients’ responses to the drug used
Our results indicate that clinically important genes are genetically highly variable and differ considerably between populations
At present regular search for and identification of functionally important polymorphisms of drug metabolism genes are under way for conducting pharmacogenetic testing (PT) since it is considered, at a given moment, one of the most important technologies in personalized medicine [5]
Summary
One of the important problems of drug therapy is variability of patients’ responses to the drug used. Genetic distinctions of a patient are the most important stable factor determining kinetics of metabolic transformations of drugs in organism and heterogeneity of individual’s reaction to a drug [2, 3]. Such distinctions are realized via polymorphic sites of protein genes involved in drug pharmacokinetics and pharmacodynamics. A. Piruzian, an individual human response to drug application is determined by a “starting state” of enzyme systems of chemical compound (xenobiotics) metabolism [4]. The PT results will allow a physician to select a drug and conditions of its dosage individually for every patient providing maximum efficiency and safety of drug therapy
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