| Autor: |
Bleecker, Eugene R., Yancey, Steven W., Baitinger, Leslie A., Edwards, Lisa D., Klotsman, Michael, Anderson, Wayne H., Dorinsky, Paul M. |
| Předmět: |
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| Zdroj: |
Journal of Allergy & Clinical Immunology; Oct2006, Vol. 118 Issue 4, p809-816, 8p |
| Abstrakt: |
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 β-receptor. However, it is not known whether similar responses occur in Arg/Arg patients receiving long-acting β2-agonists. Objective: We sought to evaluate the effects of variation in the β2-adrenergic receptor gene (ADRB2) on clinical response to salmeterol administered with fluticasone propionate. Methods: Subjects (n = 183) currently receiving short-acting β2-agonists were randomized to twice-daily therapy with salmeterol, 50 μg, administered with fluticasone propionate, 100 μg, 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 β2-adrenergic receptor do not affect patients'' responses to recommended asthma therapy with salmeterol and fluticasone propionate. [Copyright &y& Elsevier] |
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