Arg16 ADRB2 genotype increases the risk of asthma exacerbation in children with a reported use of long-acting β2-agonists: results of the PACMAN cohort

Pharmacogenomics. 2013 Dec;14(16):1965-71. doi: 10.2217/pgs.13.200.

Abstract

Background: Current evidence suggests that asthma patients with the ADRB2 Arg16 genotype have a poorer response to long-acting β2-agonists (LABA), but the results remain inconsistent.

Aim: This study assessed the association between Arg16 variants and treatment outcome in children treated with inhaled corticosteroids (ICS) and LABA.

Materials & methods: ADRB2 Arg16 was genotyped in 597 children (4-12 years of age) participating in the PACMAN cohort study. A questionnaire was used to assess asthma control, frequency of asthma-related emergency department visits and use of oral corticosteroids in the past year.

Results: Arg/Arg carriers with a reported use of ICS and LABA had an increased risk of oral corticosteroid use (odds ratio: 14.9; 95% CI: 1.59-140.1) and emergency department visits in the past year (odds ratio: 11.9; 95% CI: 1.22-115.8) compared to Gly/Gly carriers. This effect was not observed in Arg/Arg genotype carriers reporting ICS use only.

Conclusion: Children who are homozygous for ADRB2 Arg16 have an increased risk of exacerbations when treated with combined LABA and ICS.

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Anti-Asthmatic Agents / administration & dosage
  • Asthma / drug therapy*
  • Asthma / genetics*
  • Asthma / pathology
  • Child
  • Child, Preschool
  • Female
  • Genotype
  • Homozygote
  • Humans
  • Male
  • Receptors, Adrenergic, beta-2 / genetics*
  • Risk Factors
  • Treatment Outcome

Substances

  • ADRB2 protein, human
  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Anti-Asthmatic Agents
  • Receptors, Adrenergic, beta-2