The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma.
Inhaled beta-adrenergic agonists are the most commonly used medications for the treatment of asthma although there is evidence that regular use may produce adverse effects in some patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect regulation of the receptor. Smaller studies examining the effects of such polymorphisms on the response to beta-agonist therapy have produced inconsistent results. We examined whether polymorphisms at codon 16 (beta(2)-AR-16) and codon 27 (beta(2)-AR-27) of the beta(2)-AR might affect the response to regular versus as-needed use of albuterol by genotyping the 190 asthmatics who had participated in a trial examining the effects of regular versus as needed albuterol use. During the 16-wk treatment period there was a small decline in morning peak expiratory flow in patients homozygous for arginine at B(2)-AR-16 (Arg/Arg) who used albuterol regularly. This effect was magnified during a 4-wk run out period, during which all patients returned to using as-needed albuterol, so that by the end of the study Arg Arg patients who had regularly used albuterol had a morning peak expiratory flow 30. 5 +/- 12.1 L/min lower (p = 0.012) than Arg/Arg patients who had used albuterol on an as needed basis. There was no decline in peak flow with regular use of albuterol in patients who were homozygous for glycine at beta(2)-AR-16. Evening peak expiratory flow also declined in the Arg/Arg patients who used albuterol regularly but not in those who used albuterol on an as-needed basis. No significant differences in outcomes between regular and as-needed treatment were associated with polymorphisms at position 27 of the beta(2)-AR. No other differences in asthma outcomes that we investigated occurred in relation to these beta(2)-AR polymorphisms. Polymorphisms of the beta(2)-AR may influence airway responses to regular inhaled beta-agonist treatment.
Israel
E
E
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Drazen
J M
JM
Liggett
S B
SB
Boushey
H A
HA
Cherniack
R M
RM
Chinchilli
V M
VM
Cooper
D M
DM
Fahy
J V
JV
Fish
J E
JE
Ford
J G
JG
Kraft
M
M
Kunselman
S
S
Lazarus
S C
SC
Lemanske
R F
RF
Martin
R J
RJ
McLean
D E
DE
Peters
S P
SP
Silverman
E K
EK
Sorkness
C A
CA
Szefler
S J
SJ
Weiss
S T
ST
Yandava
C N
CN
D000293:Adolescent; D000420:Albuterol / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000187:drug effects*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol