Beta2-adrenergic receptor polymorphisms as a determinant of preferential bronchodilator responses to β2-agonist and anticholinergic agents in Japanese patients with chronic obstructive pulmonary disease

Background: Previous studies have shown that polymorphisms in the β2-adrenergic receptor gene (ADRB2) may influence bronchodilator response (BDR) to both β2-agonists and anticholinergics, possibly by intracellular cross-talk, but in opposite ways, in the Japanese population. We hypothesized that the preferential response to either class of bronchodilators might be determined by ADRB2 polymorphisms in patients with chronic obstructive pulmonary disease (COPD). Objective: To examine the association of ADRB2 polymorphisms and preferential BDR to β2-agonists and anticholinergics in patients with COPD. Design and participants: The participants had been enrolled in the Hokkaido COPD cohort study. BDR to either class of bronchodilators (salbutamol or oxytropium, 0.4 mg) was measured every 6 months for 2 years. Considering the variation of BDR within and between days, mean values of postbronchodilator increases in forced expiratory volume in 1 s (ΔFEV₁) for the two agents measured at two different visits were initially used for the primary analysis (N=189). To confirm the results of the primary analysis, ΔFEV₁ measured at a single visit was also used for secondary analyses. Results: Although a significant correlation between BDRs to salbutamol and to oxytropium was observed (P<0.001, r=0.36), there were individuals who responded preferentially to one of the two agents. When the participants were classified into two groups based on the bronchodilator causing the better response (salbutamol-dominant group and oxytropium-dominant group), Arg allele was significantly more common in the oxytropium-dominant group than in the salbutamol-dominant group (0.001<P<0.05). Conclusion: ADRB2 polymorphism may be a determinant of preferential BDR to either β2-agonists or anticholinergics in patients with COPD.