Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma.
BACKGROUND
Genetic variation of the beta2-adrenoceptor (ADRB2) influences receptor function in vitro. There are reports that, in vivo, bronchodilator response is related to ADRB2 genotype, and that clinical outcomes during chronic therapy with beta2-agonist drugs are also influenced by genotype. Whether these features are related to single nucleotide polymorphisms or to combinations (haplotypes) is unclear.


OBJECTIVE
Our aim was to measure bronchodilator response in patients with asthma stratified by ADRB2 haplotype. This was done after eliminating the confounding effect of prior drug treatment with inhaled beta2-agonists and corticosteroids.


METHODS
ADRB2 haplotype was determined in 176 patients with asthma, of whom 161 harbored the six most common combinations. Treatment with inhaled beta2-agonists and inhaled corticosteroids was withheld for appropriate intervals. Spirometric changes 20 minutes after a single dose of albuterol (2.5 mg by nebulizer) were then recorded.


RESULTS
There were no significant differences in bronchodilator response (% improvement in FEV(1)) with respect to any of the major ADRB2 haplotypes or genotypes.


CONCLUSIONS
Genetic variation of the ADRB2 does not influence the immediate response to inhaled beta2-agonist. The confounding effect of tolerance resulting from regular beta2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with beta2-agonists.
Taylor
D Robin
DR
Otago Respiratory Research Unit and Department of Preventive and Social Medicine, Dunedin School of Medicine, New Zealand. robin.taylor@stonebow.otago.ac.nz
Epton
Michael J
MJ
Kennedy
Martin A
MA
Smith
Andrew D
AD
Iles
Steven
S
Miller
Allison L
AL
Littlejohn
Matthew D
MD
Cowan
Jan O
JO
Hewitt
Tracey
T
Swanney
Maureen P
MP
Brassett
Karen P
KP
Herbison
G Peter
GP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology*; D001249:Asthma / Q000235:genetics / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D005260:Female; D005541:Forced Expiratory Volume; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol