title: Methacholine PC20 in African Americans and whites with asthma with homozygous genotypes at ADRB2 codon 16.
abstract: BACKGROUND
  African Americans have worse asthma outcomes compared to whites. Adrenoceptor beta 2, surface gene (ADRB2) Gly16Arg genotypes have been associated with β2-agonist bronchodilator response, asthma exacerbation rate, response to methacholine, and lung function decline but not specifically in African Americans.
  
  
  OBJECTIVE
  We sought to compare the provocative concentration of methacholine that causes a 20% fall in FEV1 (PC20) in African Americans and whites with asthma who were ADRB2 homozygous at codon 16 (Arg16Arg or Gly16Gly).
  
  
  METHODS
  African Americans and whites whose parents and grandparents were of the same race, aged ≥10 years, with baseline FEV1 of ≥60% predicted, and no upper or lower respiratory tract infection within the previous 2 weeks meeting genotype criteria were enrolled. PC20 was measured after withholding short-acting and long-acting β2-agonists for 8 and 12 h respectively, montelukast for 24 h, ipratropium bromide and inhaled corticosteroids for 12 h, and antihistamines for 72 h.
  
  
  RESULTS
  423 participants were screened and 88 had a positive challenge. Participants were 32 yrs ± 19 yrs (mean ± SD), 70% female, 51% White (vs. African American), 6% Hispanic. Similar numbers of participants were using inhaled corticosteroids by race and genotype. There were significant differences in log PC20 between race/genotype groups (p = 0.012). African American Arg16Arg participants had a lower log PC20 than White Gly16Gly (p = 0.009) and African American Gly16Gly (p = 0.041) participants. Both race and genotype contributed significantly to the model (p = 0.037 and p = 0.014, respectively) but there was no interaction between race and genotype on log PC20.
  
  
  CONCLUSIONS
  Airway hyperresponsiveness is influenced by race and the ADRB2 codon 16 polymorphism. African Americans with the Arg16Arg genotype have increased airway reactivity and may be at risk for worse asthma outcomes. Inclusion of genetic information as an additional clinical tool may aid in the personalization of asthma management decisions. [ClinicalTrials.gov Identifier: NCT00708227].
authors: Center for Pharmacogenomics and Translational Research, Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA. kblake@nemours.org
authors: Kathryn
authors: K
authors: Blake
authors: James D
authors: JD
authors: Cury
authors: Jobayer
authors: J
authors: Hossain
authors: Kelan
authors: K
authors: Tantisira
authors: Jianwei
authors: J
authors: Wang
authors: Edward
authors: E
authors: Mougey
authors: John
authors: J
authors: Lima
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000328:Adult; D001741:Black or African American; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001249:Asthma / Q000208:ethnology* / Q000235:genetics / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000494:pharmacology; D003521:Cyclopropanes; D005260:Female; D005838:Genotype; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D009241:Ipratropium / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride; D008875:Middle Aged; D011804:Quinolines / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012129:Respiratory Function Tests; D013440:Sulfides; D044465:White People; D055815:Young Adult
chemical_list: C553443:ADRB2 protein, human; D000085:Acetates; D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D003521:Cyclopropanes; D006633:Histamine Antagonists; D011804:Quinolines; D018343:Receptors, Adrenergic, beta-2; D013440:Sulfides; D016210:Methacholine Chloride; D009241:Ipratropium; C093875:montelukast
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