Asthma is a heterogeneous chronic inflammatory disease of the airways, which insufficient treatment reduces the quality of patient’s life. The effectiveness of asthma treatment, the optimal drug class and dosage are largely determined by genetic and epigenetic factors that should be considered by determining patient treatment. In recent years, significant progress in asthma pharmacogenetics has been made using the candidate genes approach, genome-wide association analysis (GWAS) and other approaches. Many genetic polymorphisms are associated with the effectiveness of therapeutic response to glucocorticosteroids, β2-agonists, and anti-leukotriene agents have been found. Epigenetic studies of asthma have identified differentially methylated regions associated with the effectiveness of asthma therapy within genes promoters. The important role of histones and miRNA modifications in drug resistance was revealed. PharmGKB (The Pharmacogenomics Knowledge Base) clinical annotation with the 2nd and 3d levels of evidence defining the role of some polymorphisms in the effectiveness of the therapeutic response were developed based on pharmacogenetic tests clinical trials. The polymorphism rs1042713 (Arg16Gly) of the ADRB2 gene is one of the most promising genetic variants that could potentially be implemented in clinical practice when prescribing short-acting β2-agonists for asthma children. The data obtained from asthma pharmacogenetic studies explain the observed variability of the therapeutic response only partially, therefore it is important to identify new informative markers using the most profound and extensive researches, such as GWAS meta-analyses, Next generation sequencing (NGS) of rare genetic variants. A comprehensive analysis of genetic and epigenetic markers with an assessment of intergenic and gene-environment interactions should be performed to increase the diagnostic value of pharmacogenetic tests, because the single effects of one or several pharmacogenetic markers to the patient’s therapeutic response is limited. To investigate the effectiveness of asthma therapy it,s necessary to conduct the clinical trials of pharmacogenetic testing and to develop clinical pharmacogenetic guidelines for using in personalize asthma therapy. This review summarizes the main pharmacogenetic studies of treatment response to the most commonly used asthma medicines: β2-agonists, inhaled corticosteroids, leukotriene modifiers and presents the current views of the epigenetic influences in asthma therapy effectiveness.

The peculiarities of distribution of hereditary pathology (HP) in the population of the Karachay-Cherkess Republic (KChR). The total number of the surveyed sample is 410 368 people representing more than 86% of the population in the region. The load of AD, AR and X-linked pathology in urban and rural populations with 21 subpopulations is estimated. The weighted average value of the load of AD, AR and X-linked pathology in the urban population (1.46±0.08, 1.19±0.07 and 0.49±0.06, respectively) is more than twice lower than in the rural population (3.76±0.16, 2.57±0.13 and 1.34±0.13, respectively). Based on the correlations between the load of HP and the main population genetic characteristics in 21 subpopulations, it is assumed that the revealed differentiation in the load of HP in different populations could be explained by the effect of genetic drift. The variety of revealed HP is represented by 230 nosological forms: 128 with inheritance type AD (954 patients from 578 families), 73 with AR (718 patients from 589 families) and 29 with X-linked (185 patients from 135 families). The analysis of the diversity of HP in accordance with the frequency of diseases showed that 15 nosological forms (AD, AR and X-linked) with a prevalence of more than 1:20000 accumulate in the majority of patients (50.31%, 68.66% and 65.95%, respectively). The revealed HP are frequent for other populations of the European part of Russia, however, some peculiarities in occurrence are determined. Fifty one disease (22 with AD, 21 with AR and 8 with X-linked type of inheritance) were registered in genetic and epidemiological studies on populations of the European part of the Russia for the first time, most of which (78.43%) belong to the group of rare and identified with a prevalence of less than 1:200000. A comparative analysis of the nosological spectrum of HP with previously studied populations of the European part of the Russia showed that several HP demonstrated marked region-specificity and accumulation in the KChR - 22 diseases (AD, AR and X-linked), which are much rarer, or do not occur in other populations of the Russian Federation.

Chronic granulomatous disease (CGD) is a hereditary disease belonging to the group of primary immunodeficiencies with impaired phagocytosis function. The most frequent is the X-linked form of CGB, which develops as a result of a molecular defect arising in the CYBB gene. The article presents the results accumulated in the Laboratory of DNA Diagnostics of the Medical Genetic Research Center during the molecular diagnosis of X-linked CGD in patients from different regions of Russia.