Salmeterol response is not affected by beta2-adrenergic receptor genotype in subjects with persistent asthma.
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 beta2-agonists.


OBJECTIVE
We sought to evaluate the effects of variation in the beta2-adrenergic receptor gene (ADRB2) on clinical response to salmeterol administered with fluticasone propionate.


METHODS
Subjects (n = 183) currently receiving short-acting beta2-agonists were randomized to twice-daily therapy with salmeterol, 50 microg, administered with fluticasone propionate, 100 microg, 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.


CONCLUSIONS
Response to salmeterol does not vary between ADRB2 genotypes after chronic dosing with an inhaled corticosteroid.


CONCLUSIONS
Analyses from this study indicate that genetic polymorphisms leading to Arg16Gly sequence changes within the beta2-adrenergic receptor do not affect patients' responses to recommended asthma therapy with salmeterol and fluticasone propionate.
Bleecker
Eugene R
ER
Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. ebleeck@wfubmc.edu
Yancey
Steven W
SW
Baitinger
Leslie A
LA
Edwards
Lisa D
LD
Klotsman
Michael
M
Anderson
Wayne H
WH
Dorinsky
Paul M
PM
D000085:Acetates / Q000008:administration & dosage; D000280:Administration, Inhalation; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000730:Androstadienes / Q000008:administration & dosage; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D005260:Female; D000068298:Fluticasone; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011804:Quinolines / Q000008:administration & dosage; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012129:Respiratory Function Tests; D000068299:Salmeterol Xinafoate; D013440:Sulfides
D000085:Acetates; D000318:Adrenergic beta-Agonists; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D011804:Quinolines; D018343:Receptors, Adrenergic, beta-2; D013440:Sulfides; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; C093875:montelukast; D000420:Albuterol