ORIGINAL RESEARCH

Analysis of the polymorphic variants of ADRB2 gene association with the β2-agonists response in patients with a rare theratype of asthma

Mdinaradze DS, Kozlov IB, Pavlova KS, Kofiadi IA, Kurbacheva OM
About authors

National Research Center Institute of Immunology of the Federal Medical-Biological Agency, Moscow, Russia

Correspondence should be addressed: Ksenia S. Pavlova
Kashirskoe shosse, 24, Moscow, 115522; moc.liamg@lacideminesk

About paper

Funding: the study was supported by the Russian Foundation for Basic Research as part of the Project #19-33-90076.

Acknowledgement: we would like to thank the Biomedicine Center for High-Precision Editing and Genetic Technologies of Pirogov Russian National Research Medical University (Moscow, Russia) for access to the molecular genetics systems.

Author contribution: Mdinaradze DS, Pavlova KS, Kurbacheva OM — selection of patients, clinical laboratory and instrumental examinations, collection of biological material; Kozlov IB, Kofiadi IA — development of the new PCR test system for analysis of the ADRB2 gene polymorphic variants, genetic testing execution.

Compliance with ethical standards: the study was approved by the ethics committee of the Institute of Immunology of the Federal Medical-Biological Agency (Minutes #13 of October 16, 2017); all patients signed voluntary consent to participate in the study.

Received: 2020-11-25 Accepted: 2020-12-09 Published online: 2020-12-27
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Standard asthma therapy includes prescription of β2-agonists. Changes in the functional activity of β2-adrenergic receptor are associated with ADRB2 gene polymorphism and related to the low therapeutic response to β2-agonists. Identification of carriers of the clinically significant gene variants will help to avoid ineffective treatment and prescribe an alternative therapy. This study aimed to assess clinical significance of the ADRB2 gene polymorphisms (Arg16Gly and Gln27Glu) associated with the therapeutic response to β2-agonists in the group of asthma patients. We subjected a small group of adult nonsmoking patients (n = 21) with moderate asthma (III–IV stage of GINA) to clinical and genetic examination. The group included patients with the new theratype, those that poorly respond to β2-adrenergic drugs but significantly to M-cholinergic agonists. The first group included patients responding well to both salbutamol and ipratropium bromide. The second group was comprised of the patients for whom salbutamol was not effective but who tested positive for response to ipratropium bromide. The analysis of distribution of polymorphic variants of Arg16Gly and Gln27Glu revealed no significant relationship between alleles and genotypes and the efficacy of β2-agonists (0.52 for the rs1042713 variant, p = 1.0; 1.0 for the rs1042714 variant, p = 0.74, respectively). The genotype of patients that did not respond to salbutamol was either Arg16Gly or Gly16Gly. Further studies are needed that would involve a larger number of patients and an expanded list of the tested polymorphic variants. 

Keywords: gene polymorphism, asthma, asthma control, β2 -adrenergic receptors, ADRB2, Arg16, Gly16, bronchodilators, short-acting β2 -agonists, SABA, short-acting anticholinergics, SAMA, long-acting anticholinergics, LABA

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