β2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate

Eugene R. Bleecker, Harold S. Nelson, Monica Kraft, Jonathan Corren, Deborah A. Meyers, Steven W. Yancey, Wayne H. Anderson, Amanda H. Emmett, Hector G. Ortega

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

Rationale: Retrospective pharmacogenetic studies have questioned whether patients with asthma who are arginine homozygous at the β2- adrenergic receptor (position 16) should use long-acting β-agonists. Objectives: To examine whether the response to salmeterol alone or in combination with an inhaled corticosteroid is influenced by β-receptor polymorphisms. Methods: Subjects using only as-needed albuterol were screened and completed two sequential open-label run-in periods (8 wk on as-needed albuterol; 8 wk on as-needed ipratropium). Five hundred forty-four subjects were randomized by Arg16Gly genotype to salmeterol alone or with fluticasone propionate for 16 weeks. Change from baseline in morning peak expiratory flow was the primary endpoint. Measurements and Main Results: Lung function responses were sustained over treatment and no statistically significant changes from baseline between genotypes within treatments were observed. Overall mean changes in morning peak flow for salmeterol with fluticasone propionate were 32.6 L/min (Arg/Arg vs. Gly/Gly, 95% confidence interval [CI], 26.3, 22.1), 25.9 L/min (Arg/Arg vs. Arg/Gly, 95% CI, 27.1, 21.3), and 24.9 L/min (Arg/Gly vs. Gly/Gly, 95%CI,213.0, 14.6), andfor salmeterol alone were 19.4 L/min (Arg/ Arg vs. Gly/Gly, 95% CI, 21.7, 21.4), 24.6 L/min (Arg/Arg vs. Arg/ Gly, 95% CI,213.0, 10.6), and 12.4 L/min (Arg/Gly vs. Gly/Gly, 95% CI, 20.2, 22.3) for Arg/Arg, Arg/Gly, and Gly/Gly genotypes, respectively. Other measures of asthma control showed similar responses. Conclusions: The results showed no evidence of a pharmacogenetic effect of β-receptor variation on salmeterol response. Clinical trial registered with www.clinicaltrials.gov (NCT 00102882).

Original languageEnglish (US)
Pages (from-to)676-687
Number of pages12
JournalAmerican journal of respiratory and critical care medicine
Volume181
Issue number7
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

Keywords

  • Arginine
  • Long-acting β-agonist
  • Pharmacogenetics
  • β-adrenergic receptor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Bleecker, E. R., Nelson, H. S., Kraft, M., Corren, J., Meyers, D. A., Yancey, S. W., Anderson, W. H., Emmett, A. H., & Ortega, H. G. (2010). β2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate. American journal of respiratory and critical care medicine, 181(7), 676-687. https://doi.org/10.1164/200809-1511OC