Abstract

Standard asthma therapy includes prescription of β2-agonists. Changes in the functional activity of β2-adrenergic receptor are associated with ADRB2 genepolymorphism and related to the low therapeutic response to β2-agonists. Identification of carriers of the clinically significant gene variants will help to avoidineffective treatment and prescribe an alternative therapy. This study aimed to assess clinical significance of the ADRB2 gene polymorphisms (Arg16Gly andGln27Glu) 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 poorlyrespond to β2-adrenergic drugs but significantly to M-cholinergic agonists. The first group included patients responding well to both salbutamol and ipratropiumbromide. The second group was comprised of the patients for whom salbutamol was not effective but who tested positive for response to ipratropium bromide. Theanalysis 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 waseither Arg16Gly or Gly16Gly. Further studies are needed that would involve a larger number of patients and an expanded list of the tested polymorphic variants.

Highlights

  • IntroductionChanges in the functional activity of β2-adrenergic receptor are associated with ADRB2 gene polymorphism and related to the low therapeutic response to β2-agonists

  • Standard asthma therapy includes prescription of β2-agonists

  • The second group (n = 7) was comprised of the patients that had poor response to salbutamol (400 μg of inhaled salbutamol causing the growth of FEV1 of less than 12% and 200 ml) and tested positive for response to 50 μg of ipratropium bromide, inhaled

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Summary

Introduction

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. 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. 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. 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.

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