title: beta-Adrenergic receptor polymorphisms and response to salmeterol.
abstract: BACKGROUND
  Several studies suggest that patients with asthma who are homozygous for arginine at the 16th position of the beta2-adrenergic receptor may not benefit from short-acting beta-agonists.
  
  
  OBJECTIVE
  We investigated whether such genotype-specific effects occur when patients are treated with long-acting beta-agonists and whether such effects are modified by concurrent inhaled corticosteroid (ICS) use.
  
  
  METHODS
  We compared salmeterol response in patients with asthma homozygous for arginine at B16 (B16Arg/Arg) with those homozygous for glycine at B16 (B16Gly/Gly) in two separate cohorts. In the first, subjects were randomized to regular therapy with salmeterol while simultaneously discontinuing ICS therapy. In the second, subjects were randomized to regular therapy with salmeterol while continuing concomitant ICS.
  
  
  RESULTS
  In both trials, B16Arg/Arg subjects did not benefit compared with B16Gly/Gly subjects after salmeterol was initiated. In the first cohort, compared with placebo, the addition of salmeterol was associated with a 51.4 L/min lower A.M. peak expiratory flow (PEF; p = 0.005) in B16Arg/Arg subjects(salmeterol, n = 12; placebo, n = 5) as compared with B16Gly/Gly subjects (salmeterol, n = 13; placebo, n = 13). In the second cohort, B16Arg/Arg subjects treated with salmeterol and ICS concurrently (n = 8) had a lower A.M. PEF (36.8 L/min difference, p = 0.048) than B16Gly/Gly subjects (n = 22) treated with the same regimen. In addition, B16 Arg/Arg subjects in the second cohort had lower FEV1 (0.42 L, p = 0.003), increased symptom scores (0.2 units, p = 0.034), and increased albuterol rescue use (0.95 puffs/d, p = 0.004) compared with B16Gly/Gly subjects.
  
  
  CONCLUSIONS
  Relative to B16Gly/Gly patients with asthma, B16Arg/Arg patients with asthma may have an impaired therapeutic response to salmeterol in either the absence or presence of concurrent ICS use. Investigation of alternate treatment strategies may benefit this group.
authors.affiliation: Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.forename: Erik
authors.initials: E
authors.lastname: Lehman
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Lazarus
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Homer A
authors.initials: HA
authors.lastname: Boushey
authors.forename: Aaron
authors.initials: A
authors.lastname: Deykin
authors.forename: John V
authors.initials: JV
authors.lastname: Fahy
authors.forename: Christine A
authors.initials: CA
authors.lastname: Sorkness
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Chinchilli
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
authors.forename: Emily
authors.initials: E
authors.lastname: DiMango
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.forename: Frank
authors.initials: F
authors.lastname: Leone
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Szefler
authors.forename: Wenlei
authors.initials: W
authors.lastname: Liu
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D000068299:Salmeterol Xinafoate; D014221:Triamcinolone / Q000008:administration & dosage
chemical_list: D000318:Adrenergic beta-Agonists; D005938:Glucocorticoids; D011943:Receptors, Adrenergic, beta; D014221:Triamcinolone; D000068299:Salmeterol Xinafoate; D000420:Albuterol