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

Authors: Carroll, CL  Stoltz, P  Schramm, CM  Zucker, AR 
Citation: Carroll CL, etal., Chest. 2009 May;135(5):1186-92. Epub 2008 Nov 24.
Pubmed: (View Article at PubMed) PMID:19029431
DOI: Full-text: DOI:10.1378/chest.08-2041

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.

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CRRD Object Information
CRRD ID: 4145092
Created: 2010-10-25
Species: All species
Last Modified: 2010-10-25
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.