Effectiveness of BA treatment depends on multiple factors, including genetic. Gln27Glu polymorphism in the ADRB2 gene is the most common and well-known.
Study Objectives: to optimize treatment in BA patients with regard to Gln27Glu polymorphism in the ADRB2 gene.
Materials and Methods: 195 patients with bronchial asthma have been examined. Patients were divided into two groups according to the dosing: group I – 164 patients receiving low doses; group II – 25 patients receiving medium doses in terms of the equivalent amount of budesonide. Control level was determined by means of Asthma Control Questionnaire and measurements of forced expiratory volume in 1 second (FEV1) before and after dose corrections of inhaled GCs and LABA. In case of poor asthma control, treatment correction was performed as follows: the patients receiving low doses of inhaled GCs and LABA (< 400 μg per day) had their doses increased to medium doses (400−800 μg per day); the patients receiving medium doses had their doses increased to high doses (> 800 μg per day). The treatment lasted 4 weeks. Further study consisted in comparative analysis of clinical efficacy of background therapy in patients who did not achieve asthma control and were additionally given 24 μg formoterol – in group A, and 18 μg tiotroprium bromide – in group B. Control level was evaluated after 4 weeks. Gln27Glu (rs1042714) polymorphism in the ADRB2 gene was detected using polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism by means of separation with agarose gel electrophoresis. To compare the groups before and after treatment correction, Wilcoxon signed-rank test was used.
Results: Control level evaluation after treatment correction showed that Glu27Glu genotype carriers in the group I had no improvement in BA control (р = 0.2 by Wilcoxon), while Gln27Gln and Gln27Glu genotype carriers (р = 0.04 and р = 0.001 by Wilcoxon) improved BA control, which was confirmed by FEV1 values (Fig. 1). Thus, there was no difference in FEV1 values before and after treatment correction (р = 0.8 by Wilcoxon) in Glu27Glu genotype carriers in group I, while Gln27Gln and Gln27Glu genotype carriers (р = 0.01 and р = 0.001 by Wilcoxon) had their FEV1 values increased. Patients in group II demonstrated no significant improvement in control level with regard to the genotypes of Gln27Glu polymorphism in the ADRB2 gene. As for FEV1 values, they were increased in Gln27Gln and Gln27Glu genotype carriers (р = 0.048 and р = 0.004 by Mann-Whitney), while Glu27Glu genotype carriers had no difference in FEV1 values (р = 0.5). Significant increase in FEV1 values was observed in Gln27Gln genotype carriers in group А (р = 0.048 by Wilcoxon) and in Gln27Gln, Gln27Glu and Glu27Glu genotype carriers in group B (р = 0.033, р = 0.003 and р = 0.007 by Wilcoxon), while in Gln27Glu and Glu27Glu genotype carriers (group A) this difference was absent (р = 0.1 and р = 0.07 by Wilcoxon).
Conclusions: It was proved that Glu27Glu genotype carriers had worse control level as compared to Gln27Gln and Gln27Glu genotype carriers; high doses of inhaled GCs and LABA in combination with tiotroprium bromide in the carriers of Glu27Glu genotype of Gln27Glu polymorphism in the ADRB2 gene is more effective in achieving control over the disease than additional formoterol 24 μg per day.
Keywords: bronchial asthma, β2-adrenergic receptor gene, Gln27Glu polymorphism, control level, long-acting β2-agonists, inhaled corticosteroids.
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