Adrenergic β2-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol

Background: On-demand inhaled albuterol is commonly prescribed worldwide. We have shown that the Arg16 allele of the adrenergic beta(2)-receptor agonist gene (ADRB2) predisposes to exacerbations in young asthmatic patients taking regular salmeterol. Objective: We have now extended our previous population by 636 patients and explored the role of the Arg16 allele on asthma exacerbations in the context of the use of on-demand albuterol and regular salmeterol. Methods: Arg/Gly status at position 16 of ADRB2 was assessed in 1182 young asthmatic patients (age, 3-22 years) from Scotland. Asthma exacerbations, use of beta-agonists and other medications over the previous 6 months, and lung function were also studied. Results: An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95% CI, 1.09-1.55; P = .003). This appears to be largely due to exposure to beta(2)-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64; 95% CI, 1.22-2.20; P =.001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled beta(2)-agonists less than once a day (OR, 1.08; 95% CI, 0.85-1.36; P =.525). The Arg16 genotype-associated risk for exacerbations was significantly different in those exposed to beta(2)-agonists daily versus those that were not (test for interaction, P =.022). Conclusion: The Arg16 genotype of ADRB2 is associated with exacerbations in asthmatic children and young adults exposed daily to beta(2)-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol. (J Allergy Clin Immunol 2009;124:1188-94.)