title: A pharmacogenetic study of ADRB2 polymorphisms and indacaterol response in COPD patients.
abstract: Genetic variation in the ADRB2 gene has been hypothesized to have a role in differential response to beta-agonist (BA) therapy in asthma. However, study results have been inconsistent and the issue remains controversial. Furthermore, the impact of ADRB2 genetic variation on BA response in chronic obstructive pulmonary disease (COPD) patients has not been thoroughly studied. We carried out a large pharmacogenetic analysis testing for an association between common ADRB2 polymorphisms and indacaterol response in COPD patients. A total of 648 indacaterol-treated patients enrolled in two large randomized phase III studies were genotyped for the most commonly studied polymorphisms in the ADRB2 gene: Gly16Arg, Gln27Glu, Thr164Ile, and a variant in the 5' untranslated region (rs1042711). Our analysis showed little evidence for the association between these ADRB2 variants and indacaterol response, suggesting that ADRB2 genetic variation is unlikely to have a major role in differential response to indacaterol treatment in COPD patients.
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
authors.forename: R
authors.initials: R
authors.lastname: Yelensky
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: S
authors.initials: S
authors.lastname: Lewitzky
authors.forename: E
authors.initials: E
authors.lastname: Leroy
authors.forename: C
authors.initials: C
authors.lastname: Hurwitz
authors.forename: D
authors.initials: D
authors.lastname: Rodman
authors.forename: A
authors.initials: A
authors.lastname: Trifilieff
authors.forename: C A
authors.initials: CA
authors.lastname: Paulding
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000235:genetics; D015363:Quinolones / Q000627:therapeutic use*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D007189:Indans; D015363:Quinolones; D018343:Receptors, Adrenergic, beta-2; C510790:indacaterol