Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol.
BACKGROUND
On-demand inhaled albuterol is commonly prescribed worldwide. We have shown that the Arg16 allele of the adrenergic beta(2)-receptor agonist gene (ADRB2) predisposes to exacerbations in young asthmatic patients taking regular salmeterol.


OBJECTIVE
We have now extended our previous population by 636 patients and explored the role of the Arg16 allele on asthma exacerbations in the context of the use of on-demand albuterol and regular salmeterol.


METHODS
Arg/Gly status at position 16 of ADRB2 was assessed in 1182 young asthmatic patients (age, 3-22 years) from Scotland. Asthma exacerbations, use of beta-agonists and other medications over the previous 6 months, and lung function were also studied.


RESULTS
An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95% CI, 1.09-1.55; P = .003). This appears to be largely due to exposure to beta(2)-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting beta(2)-agonist treatment (OR, 1.64; 95% CI, 1.22-2.20; P = .001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled beta(2)-agonists less than once a day (OR, 1.08; 95% CI, 0.85-1.36; P = .525). The Arg16 genotype-associated risk for exacerbations was significantly different in those exposed to beta(2)-agonists daily versus those that were not (test for interaction, P = .022).


CONCLUSIONS
The Arg16 genotype of ADRB2 is associated with exacerbations in asthmatic children and young adults exposed daily to beta(2)-agonists, regardless of whether the exposure is to albuterol or long-acting agonists, such as salmeterol.
Royal Alexandra Children's Hospital, Brighton and Sussex Medical School, Brighton, United Kingdom.
Kaninika
K
Basu
Colin N A
CN
Palmer
Roger
R
Tavendale
Brian J
BJ
Lipworth
Somnath
S
Mukhopadhyay
D000280:Administration, Inhalation; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists; D000420:Albuterol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000483:Alleles; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D000068299:Salmeterol Xinafoate; D055815:Young Adult
D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000068299:Salmeterol Xinafoate; D000420:Albuterol