Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing.

摘要: The beta2-adrenergic receptor (beta2AR) agonists are the most widely used agents in treatment of asthma, but genetic determinants responsiveness to these unknown. Two polymorphic loci within coding region beta2AR have been recently described at amino acids 16 and 27. It has reported that glycine codon (Gly-16) is associated with increased agonist-promoted downregulation as compared arginine-16 (Arg-16). form glutamic acid 27 (Glu-27), on other hand, shown be resistant when glutamine-27 (Gln-27), only coexpressed Arg-16. To assess if different genotypes two polymorphisms would show differential responses inhaled agonists, we genotyped 269 children who were participants a longitudinal study asthma. Spirometry was performed before after administration 180 microg albuterol, positive response considered an increase >15.3% predicted FEV1. There marked linkage disequilibrium between polymorphisms, 97.8% all chromosomes carried Arg-16 also carrying Gln-27. When homozygotes for Gly-16, 5.3 times (95% confidence interval 1.6-17.7) heterozygotes beta2AR-16 2.3 (1.3-4.2) more likely respond respectively. Similar trends observed asthmatic nonasthmatic children, results independent baseline lung function, ethnic origin, previous use antiasthma medication. No association found beta2AR-27 polymorphism albuterol. These may explain some variability therapeutic doses albuterol children.