title: Do genetic polymorphisms alter patient response to inhaled bronchodilators?
abstract: BACKGROUND
  Short- and long-acting β agonists (SABA and LABA) are bronchodilators for treating asthma. Bronchodilator response (BDR) is quantified by measuring air expired in the first second during a forced expiratory maneuver, prior to and following inhalation of SABA. BDR has been associated with a significant degree of heterogeneity, in part attributable to genetic variation. Heritability, the proportion of phenotypic variability accounted for by genetic variation is estimated to account for 50% of pulmonary function and 28.5% for BDR.
  
  
  METHODS
  A MEDLINE search for English articles published from January 1990 to June 2014 was completed using the terms: bronchodilator, bronchodilator response, short-acting bronchodilator, long-acting bronchodilator, β2 adrenergic receptor gene (ADRB2), asthma and pharmacogenomics. The effects of ADRB2 variants on BDR and the safety of SABA and LABA + inhaled corticosteroids have been studied with equivocal results. Single and candidate gene studies have identified variants in other genes that alter response to bronchodilators. Associations were recently observed between hospital admission rates and two rare ADRB2 polymorphisms: Thr164Ile and a 25 base pair insertion-deletion at nucleotide -376. This was the first report of life-threatening events associated with LABA being linked to rare ADRB2 variants.
  
  
  CONCLUSIONS
  Pharmacogenomic studies over the last two decades clearly demonstrate that polymorphisms alter patient response to bronchodilators in patients with asthma.
authors.affiliation: Center for Pharmacogenomics and Translational Research, Nemours Children's Clinic , 807 Children's Way, Jacksonville, FL 32207 , USA , +1 904 697 3683 ; +1 904 687 7988 ; jlima@nemours.org.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lima
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D012129:Respiratory Function Tests
chemical_list: C553443:ADRB2 protein, human; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D018343:Receptors, Adrenergic, beta-2
keywords: adrenergic receptor; asthma; bronchodilator; drug; gene; heritability; heterogeneity; pharmacogenetic; polymorphisms; response