Beta2-adrenoceptor polymorphisms predict response to beta2-agonists in children with acute asthma.
The aim of this study was to determine the influence of single nucleotide polymorphisms in the beta(2)-adrenoceptor gene, on the response to inhaled beta(2)-agonists in children with acute asthma. We hypothesised that children with polymorphisms that generate enhanced receptor downregulation in vitro, Gly16 and Gln27, would have a slower response to beta(2)-agonist therapy during acute asthma. One hundred and forty-eight children with acute asthma were recruited and genotyped for beta(2)Arg16Gly and beta(2)Gln27Glu. For Gln27Glu, individuals Gln27Gln took longest to stretch out to 1, 2 and 4 hourly beta(2)-agonists, followed by heterozygotes who were intermediate and Glu27Glu who responded most rapidly (1 hourly: 2.6 hr vs. 2.0 vs. 1.4, p = 0.02; 2 hourly: 10.6 hr vs. 10.7 vs. 6.8, p = 0.07; 4 hourly: 29.8 hr vs. 28.5 vs. 24.3, p = 0.30). The ability to prospectively identify children who respond less effectively to beta (2)-agonists during an acute asthma attack has the potential to allow the generation of genotype-specific treatment pathways.
School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia.
Andrew C
AC
Martin
Guicheng
G
Zhang
Kristina
K
Rueter
Siew-Kim
SK
Khoo
Joelene
J
Bizzintino
Catherine M
CM
Hayden
Gary C
GC
Geelhoed
Jack
J
Goldblatt
Ingrid A
IA
Laing
Peter N
PN
Le Souëf
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011336:Probability; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2