Salmeterol response is not affected by β2-adrenergic receptor genotype in subjects with persistent asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:118

Article

Bleecker, Eugene R. ; Yancey, Steven W. ; Baitinger, Leslie A. ; Edwards, Lisa D. ; Klotsman, Michael ; Anderson, Wayne H. ; Dorinsky, Paul M.

关键词: asthma;    salmeterol xinafoate;    genotype;    polymorphism (genetics);    receptors;    beta(2);    adrenergic;    fluticasone propionate;   

DOI  :  10.1016/j.jaci.2006.06.036

来源: Elsevier

【 摘 要 】

Background: Recent studies suggest that there might be an association between albuterol use and worsening asthma in patients homozygous for arginine (Arg/Arg) at codon 16 of the beta-receptor. However, it is not known whether similar responses occur in Arg/Arg patients receiving long-acting beta(2)-agonists. Objective: We sought to evaluate the effects of variation in the beta(2)-adrenergic receptor gene (ADRB2) on clinical response to salmeterol administered with fluticasone propionate. Methods: Subjects (n=183) currently receiving short-acting beta(2)-agonists were randomized to twice-daily therapy with salmeterol, 50 mu g, administered with fluticason propionate, 100 mu g, in a single inhaler or daily therapy with montelukast for 12 weeks, followed by a 2- to 4-day run-out period. Results: There was sustained and significant improvement (P <.001) over baseline in all measures of asthma control in subjects receiving salmeterol, regardless of Arg16Gly genotype. Morning peak expiratory flow in subjects with the Arg/Arg genotype showed 89.0 +/- 16.1 L/min improvement over baseline compared with 93.7 +/- 12.7 L/min for Gly/Gly subjects and 92.5 +/- 11.9 L/min for Arg/Gly subjects. Pairwise changes were similar for Arg/Arg compared with Gly/Gly or Arg/Gly genotypes (estimated differences, 4.7 L/min and 3.5 L/min, respectively). Responses did not appear to be modified by haplotype pairs. During the run-out period, all subjects had predictable and similar decreases in measures of asthma control, with no differences between genotypes. Conclusion: Response to salmeterol does not vary between ADRB2 genotypes after chronic dosing with an inhaled corticosteroid. Clinical implications: Analyses from this study indicate that genetic polymorphisms leading to Arg16Gly sequence changes within the beta(2)-adrenergic receptor do not affect patients' responses to recommended asthma therapy with salmeterol and fluticasone propionate.

【 授权许可】

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