Methacholine PC20 In African Americans And Whites With Asthma With Homozygous Genotypes At ADRB2 Codon 16

BACKGROUND—African Americans have worse asthma outcomes compared to whites. Adrenoceptor beta 2, surface gene (ADRB2) Gly16Arg genotypes have been associated with β2© 2013 Elsevier Ltd. All rights reserved. Corresponding Author: Kathryn Blake, PharmD. , Nemours Children’s Clinic, 807 Children’s Way, Jacksonville, FL 32207 USA, Telephone: (904) 697-3806, Fax: (904) 697-3799, kblake@nemours.org. All work was performed in the Center for Pharmacogenomics and Translational Research, Nemours Children’s Clinic, Jacksonville, FL, USA. Financial Disclosures and Conflicts of Interest: Kathryn Blake, PharmD has no conflicts of interest to report. J Davis Cury, MD has no conflicts of interest to report. Jobayer Hossain, PhD has no conflicts of interest to report. Kelan Tantisira, MD has no conflicts of interest to report. Jianwei Wang, MD has no conflicts of interest to report. Ed Mougey, PhD has no conflicts of interest to report. John Lima, PharmD has no conflicts of interest to report. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Pulm Pharmacol Ther. Author manuscript; available in PMC 2014 June 01. Published in final edited form as: Pulm Pharmacol Ther. 2013 June ; 26(3): 342–347. doi:10.1016/j.pupt. 2013.01. 009. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript 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 codon16 (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 hours respectively, montelukast for 24 hours, ipratropium bromide and inhaled corticosteroids for 12 hours, and antihistamines for 72 hours. RESULTS—423 participants were screened and 88 had a positive challenge. Participants were 32yrs ± 19yrs (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 AND CLINICAL RELEVANCE—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].