Beta2-adrenergic receptor polymorphisms affect response to treatment in children with severe asthma exacerbations.
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.
Carroll
Christopher L
CL
Department of Pediatrics, Connecticut Children's Medical Center, Hartford, CT. Electronic address: ccarrol@ccmckids.org.
Stoltz
Petronella
P
Department of Pediatrics, Connecticut Children's Medical Center, Hartford, CT.
Schramm
Craig M
CM
Department of Pediatrics, Connecticut Children's Medical Center, Hartford, CT.
Zucker
Aaron R
AR
Department of Pediatrics, Connecticut Children's Medical Center, Hartford, CT.
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000420:Albuterol / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005838:Genotype; D018698:Glutamic Acid / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006801:Humans; D007902:Length of Stay; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D005973:Glutamine; D018698:Glutamic Acid; D000420:Albuterol; D005998:Glycine