PHARMACOGENETICS OF ASTHMA

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.

бронхиальная астма, фармакогенетика, эпигенетика, терапия, ген, bronchial asthma, pharmacogenetics, epigenetics, therapy, gene