Beta2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate.
BACKGROUND
Retrospective pharmacogenetic studies have questioned whether patients with asthma who are arginine homozygous at the beta(2-)adrenergic receptor (position 16) should use long-acting beta-agonists.


OBJECTIVE
To examine whether the response to salmeterol alone or in combination with an inhaled corticosteroid is influenced by beta- 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.


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], -6.3, 22.1), 25.9 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -7.1, 21.3), and 24.9 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -13.0, 14.6), and for salmeterol alone were 19.4 L/min (Arg/Arg vs. Gly/Gly, 95% CI, -1.7, 21.4), 24.6 L/min (Arg/Arg vs. Arg/Gly, 95% CI, -13.0, 10.6), and 12.4 L/min (Arg/Gly vs. Gly/Gly, 95% CI, -0.2, 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 beta-receptor variation on salmeterol response. Clinical trial registered with www.clinicaltrials.gov (NCT 00102882).
Bleecker
Eugene R
ER
Center for Human Genomics and Department of Medicine, Wake Forest University Health Sciences, Winston Salem, North Carolina, USA.
Nelson
Harold S
HS
Kraft
Monica
M
Corren
Jonathan
J
Meyers
Deborah A
DA
Yancey
Steven W
SW
Anderson
Wayne H
WH
Emmett
Amanda H
AH
Ortega
Hector G
HG
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage*; D001120:Arginine / Q000235:genetics; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D005260:Female; D000068298:Fluticasone; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D000068299:Salmeterol Xinafoate; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D001120:Arginine; D000068298:Fluticasone; D000420:Albuterol; D005998:Glycine