Beta2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations

Chest. 2009 May;135(5):1186-1192. doi: 10.1378/chest.08-2041. Epub 2008 Nov 24.


Background: beta(2)-adrenergic receptor (AR) agonists are the mainstay of treatment for severe asthma exacerbations, one of the most common causes of critical illness in children. Genotypic differences in the beta(2)-AR gene, particularly at amino acid positions 16 and 27, have been shown to affect the response to beta(2)-AR agonist therapy. Our hypothesis is that genotypic differences contribute to patient response to beta(2)-AR agonist treatment during severe asthma exacerbations in children.

Methods: Children admitted to the hospital ICU for a severe asthma exacerbation between 2002 and 2005 were located, and genetic samples were obtained from saliva. Children hospitalized during this period were treated with a protocol that titrated beta(2)-AR therapy (first nebulized, then IV) according to a validated clinical asthma score.

Results: Thirty-seven children hospitalized during the study period were enrolled into the study. At amino acid position 16 in the beta(2)-AR gene, 13 children were homozygous for the glycine (Gly) allele (Gly/Gly), 8 were homozygous for the arginine (Arg) allele (Arg/Arg), and 16 were heterozygous (Arg/Gly). Despite similar clinical asthma scores on hospital admission, the children with the Gly/Gly genotype had significantly shorter hospital ICU length of stay and duration of continuously nebulized albuterol therapy and were significantly less likely to require IV beta(2)-AR therapy than those with Arg/Arg or Arg/Gly genotypes. No association existed among polymorphisms at amino acid position 27 and response to beta(2)-AR therapy.

Conclusions: In this cohort of children with severe asthma exacerbations, children whose genotypes were homozygous for Gly at amino acid position 16 of the beta(2)-AR gene had a more rapid response to beta(2)-AR agonist treatment. The beta(2)-AR genotype appears to influence the response to therapy in this population.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adrenergic beta-Agonists / administration & dosage*
  • Albuterol / administration & dosage*
  • Asthma / drug therapy*
  • Asthma / genetics*
  • Asthma / pathology
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Genotype
  • Glutamic Acid / genetics
  • Glutamine / genetics
  • Glycine / genetics
  • Humans
  • Length of Stay
  • Male
  • Polymorphism, Single Nucleotide*
  • Receptors, Adrenergic, beta-2 / genetics*
  • Retrospective Studies
  • Severity of Illness Index
  • Treatment Outcome


  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta-2
  • Glutamine
  • Glutamic Acid
  • Albuterol
  • Glycine