Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment

S. Turner (Lead / Corresponding author), Ben Francis, Susanne Vijverberg, Maria Pino-Yanes, Anke H. Maitland-van der Zee, Kaninika Basu, Lauren Bignell, Somnath Mukhopadhyay, Roger Tavendale, Colin Palmer, Daniel Hawcutt, Munir Pirmohamed, Esteban G. Burchard, Brian Lipworth

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Abstract

Background: 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. Objectives: 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. 

Methods: 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. 

Results: 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).

Conclusions: 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.

Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume138
Issue number1
Early online date7 Jan 2016
DOIs
Publication statusPublished - Jul 2016

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Keywords

  • Adrenergic receptors
  • Asthma
  • Child
  • Disease exacerbation
  • Therapeutics

Cite this

Turner, S., Francis, B., Vijverberg, S., Pino-Yanes, M., Maitland-van der Zee, A. H., Basu, K., Bignell, L., Mukhopadhyay, S., Tavendale, R., Palmer, C., Hawcutt, D., Pirmohamed, M., Burchard, E. G., & Lipworth, B. (2016). Childhood asthma exacerbations and the Arg16 β2-receptor polymorphism: A meta-analysis stratified by treatment. Journal of Allergy and Clinical Immunology, 138(1), 107-113. https://doi.org/10.1016/j.jaci.2015.10.045