β₂-Adrenoceptor Polymorphisms Predict Response to β₂-Agonists in Children with Acute Asthma

Abstract

The aim of this study was to determine the influence of single nucleotide polymorphisms in the β₂-adrenoceptor gene, on the response to inhaled β₂-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 β₂-agonist therapy during acute asthma. One hundred and forty-eight children with acute asthma were recruited and genotyped for β₂Arg16Gly and β₂Gln27Glu. For Gln27Glu, individuals Gln27Gln took longest to stretch out to 1, 2 and 4 hourly β₂-agonists, followed by heterozygotes who were intermediate and Glu27Glu who responded most rapidly (1hourly: 2.6hr vs. 2.0 vs. 1.4, p = 0.02; 2 hourly: 10.6hr vs. 10.7 vs. 6.8, p = 0.07; 4 hourly: 29.8hr vs. 28.5 vs. 24.3, p = 0.30). The ability to prospectively identify children who respond less effectively to β ₂-agonists during an acute asthma attack has the potential to allow the generation of genotype-specific treatment pathways.

Keywords:

• asthma genetics
• β₂ agonists
• childhood asthma
• β₂AR polymorphisms