PERINATOLOGIYA AND PEDIATRIYA.2019.2(78):38-45; doi 10.15574/PP.2019.78.38

Livshits L. A., Tatarsky P. F., Gorodna O. V., Mayakovskaya A. V., Volynets G. P., Chumachenko N. G., Umanets T. R., Lapshin V. F., Antipkin Yu. G.
Institute of Molecular Biology and Genetics, NAS of Ukraine, Kyiv
SI «Institute of Pediatrics, Obstetrics and Gynecology named after acad. O.M. Lukyanova NAMS of Ukraine», Kyiv

Purpose — to investigate the association of the C79G polymorphism of the ADRB2 gene with the risk of developing Bronchial asthma (BA) in children living under different environmental conditions and to generate in silico 3D structures of β2-adrenoreceptor isoformsencoded by polymorphic variants of the ADRB2 gene (A46G, C79G, and C491T) in order to predict conformational changes which can impact the interaction with salbutamol.

Patients and methods. 114 children aged 3 to 18 years with BA of moderate to severe, controlled course, were randomized into two groups: group I (children from conditionally pure region of Kyiv and Kyiv region) and group II (children from ecologically polluted region). The control group climbed 86 unrelated healthy adults from different regions of Ukraine. The polymorphic variant of the ADRB2 gene (C79G) was investigated by the allelic-specific polymerase chain reaction. The computermodeling of the 3D β2-adrenergic protein structure homology was performed using SWISS-MODEL and I-TASSER web servers, molecular docking was performed using the AutoDock Vina program.

Results. It was found that the frequency of the polymorphic variant 79G of the ADRB2 genecarriersis statistically significantly higher (p<0.05) in the group II (69.4%) compared with the control group (55.8%). According to the analysis of the spatial structure of the ADRB2 protein, it was determined that p.16Arg> Gly and p.27Gln>Glu substitutions localized on the N-terminal sequence, and can affect interaction with protein partners, in turn the amino acid substitution p.164Thr> Ile is localized near the ligand binding site and may reduce the affinity of salbutamol for the corresponding mutant receptor.

Conclusions. The polymorphic variant of 79G of the ADRB2 gene can be considered as a factor of the hereditary susceptibility of BA developmentin conditions of environmentalanthropogenic loading. The 491C>T ADRB2 gene mononucleotide substitution can be considered as a pharmacogenetic marker of a poor patient response to treatment with salbutamol.

Key words: asthma, children, polymorphism of β2-adrenoreceptor gene, salbutamol.

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Article received: Feb 02, 2019. Accepted for publication: May 25, 2019.