title: Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment.
abstract: The Gly-to-Arg substitution at the 16 position (rs1042713) in the β2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of β2-receptors.
  
  
  
  We sought to undertake a meta-analysis to test the hypothesis that there is an interaction between the A allele of rs1042713 (Arg16 amino acid) and long-acting β-agonist (LABA) exposure for asthma exacerbations in children.
  
  
  
  Children with diagnosed asthma were recruited in 5 populations (BREATHE, Genes-Environments and Admixture in Latino Americans II, PACMAN, the Paediatric Asthma Gene Environment Study, and the Pharmacogenetics of Adrenal Suppression with Inhaled Steroid Study). A history of recent exacerbation and asthma treatment was determined from questionnaire data. DNA was extracted, and the Gly16Arg genotype was determined.
  
  
  
  Data from 4226 children of white Northern European and Latino origin were analyzed, and the odds ratio for exacerbation increased by 1.52 (95% CI, 1.17-1.99; P = .0021) for each copy of the A allele among the 637 children treated with inhaled corticosteroids (ICSs) plus LABAs but not for treatment with ICSs alone (n = 1758) or ICSs plus leukotriene receptor antagonist (LTRAs; n = 354) or ICSs plus LABAs plus LTRAs (n = 569).
  
  
  
  The use of a LABA but not an LTRA as an "add-on controller" is associated with increased risk of asthma exacerbation in children carrying 1 or 2 A alleles at rs1042713. Prospective genotype-stratified clinical trials are now required to explore the potential role of rs1042713 genotyping for personalized asthma therapy in children.
authors.affiliation: Child Health, University of Aberdeen, Aberdeen, United Kingdom. Electronic address: s.w.turner@abdn.ac.uk.
authors.forename: Steve
authors.initials: S
authors.lastname: Turner
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Francis
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Susanne
authors.initials: S
authors.lastname: Vijverberg
authors.affiliation: CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pino-Yanes
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, University of Utrecht, Utrecht, The Netherlands.
authors.forename: Anke H
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.affiliation: Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Kaninika
authors.initials: K
authors.lastname: Basu
authors.affiliation: Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Brighton and Sussex Medical School, Brighton, United Kingdom.
authors.forename: Lauren
authors.initials: L
authors.lastname: Bignell
authors.affiliation: Academic Department of Paediatrics, Royal Alexandra Children's Hospital, Brighton and Sussex Medical School, Brighton, United Kingdom; Population Pharmacogenetics Group, University of Dundee, Dundee, United Kingdom.
authors.forename: Somnath
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Population Pharmacogenetics Group, University of Dundee, Dundee, United Kingdom.
authors.forename: Roger
authors.initials: R
authors.lastname: Tavendale
authors.affiliation: Population Pharmacogenetics Group, University of Dundee, Dundee, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Palmer
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hawcutt
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and Medicine, University of California, San Francisco, Calif; Center for Genes, Environment and Health, University of California, San Francisco, Calif.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: Asthma and Allergy Research Group, University of Dundee, Dundee, United Kingdom.
authors.forename: Brian
authors.initials: B
authors.lastname: Lipworth
mesh_terms: D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000627:therapeutic use; D000483:Alleles; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001120:Arginine / Q000737:chemistry / Q000235:genetics*; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics*; D012307:Risk Factors
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D003062:Codon; D020024:Leukotriene Antagonists; D018343:Receptors, Adrenergic, beta-2; D001120:Arginine
keywords: Adrenergic receptors; asthma; child; disease exacerbation; therapeutics