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

Steve Turner, 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

Keywords

  • adrenergic receptors
  • asthma
  • child
  • disease exacerbation
  • therapeutics

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    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