Effect of polymorphism of the beta(2)-adrenergic receptor on response to regular use of albuterol in asthma.
BACKGROUND
Regular use of inhaled beta-adrenergic agonists may have adverse effects in some asthma patients. Polymorphisms of the beta(2)-adrenergic receptor (beta(2)-AR) can affect its regulation; however, results of smaller studies of the effects of such polymorphisms on response to beta-agonist therapy have been inconsistent.


METHODS
We examined the possible effects of polymorphisms at codons 16 (beta(2)-AR-16) and 27 (beta(2)-AR-27) on response to albuterol by genotyping 190 asthmatics who had participated in a trial of regular versus as-needed albuterol use.


RESULTS
During the 16-week treatment period, patients homozygous for arginine (Arg/Arg) at beta(2)-AR-16 who used albuterol regularly had a small decline in morning peak expiratory flow (AM PEF). This effect was magnified during a 4-week run-out period, when all patients returned to as-needed albuterol only. By the end of the study, Arg/Arg subjects who had used albuterol regularly had an AM PEF 30.5 +/- 12.1 liters/min lower (p = 0.012) than Arg/Arg patients who had used albuterol as needed only. Subjects homozygous for glycine at beta(2)-AR-16 showed no such decline. Evening PEF also declined in the Arg/Arg regular but not in as-need albuterol users. No significant differences between regular and as-needed treatment were associated with polymorphisms at beta(2)-AR-27.


CONCLUSIONS
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, MA 02115, USA. eisrael@rics.bwh.harvard.edu
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D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D000420:Albuterol