Childhood asthma exacerbations and the Arg16 b2-receptor polymorphism: a meta-analysis stratified by treatment

Turner, Steve, Francis, Ben, Vijverberg, Susanne, Pino-Yanes, Maria, Maitland-van der Zee, Anke H, Basu, Kaninika, Bignell, Lauren, Mukhopadhyay, Somnath, Tavendale, Roger, Palmer, Colin, Hawcutt, Daniel, Pirmohamed, Munir, Burchard, Esteban G and Lipworth, Brian (2016) Childhood asthma exacerbations and the Arg16 b2-receptor polymorphism: a meta-analysis stratified by treatment. Journal of Allergy and Clinical Immunology, 138 (1). 107-113.e5. ISSN 0091-6749

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Abstract

Background: The Gly-to-Arg substitution at the 16 position
(rs1042713) in the b2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of b2-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 b-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 5 .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 5 1758) or ICSs plus leukotriene receptor antagonist (LTRAs; n 5 354) or ICSs plus LABAs plus LTRAs (n 5 569). Conclusions: The use of a LABA but not an LTRA as an ‘‘addon 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. (J Allergy Clin Immunol 2016

Item Type: Article
Keywords: Adrenergic receptors, asthma, child, disease exacerbation, therapeutics
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects: R Medicine > RJ Pediatrics
R Medicine > RJ Pediatrics > RJ0047.3 Genetic aspects
Depositing User: Judy Keogh
Date Deposited: 23 Feb 2016 11:27
Last Modified: 29 Sep 2017 09:50
URI: http://sro.sussex.ac.uk/id/eprint/59739

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