TY - JOUR
T1 - Childhood asthma exacerbations and the Arg16 beta(2)-receptor polymorphism: A meta-analysis stratified by treatment
AU - Turner, Steve
AU - Francis, Ben
AU - Vijverberg, Susanne
AU - Pino-Yanes, Maria
AU - Maitland-van der Zee, Anke H.
AU - Basu, Kaninika
AU - Bignell, Lauren
AU - Mukhopadhyay, Somnath
AU - Tavendale, Roger
AU - Palmer, Colin
AU - Hawcutt, Daniel
AU - Pirmohamed, Munir
AU - Burchard, Esteban G.
AU - Lipworth, Brian
PY - 2016
Y1 - 2016
N2 - Background: The Gly-to-Arg substitution at the 16 position (rs1042713) in the beta(2)-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of beta(2)-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 beta-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 from4226 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 5 354) or ICSs plus LABAs plus LTRAs (n = 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
AB - Background: The Gly-to-Arg substitution at the 16 position (rs1042713) in the beta(2)-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of beta(2)-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 beta-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 from4226 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 5 354) or ICSs plus LABAs plus LTRAs (n = 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
U2 - https://doi.org/10.1016/j.jaci.2015.10.045
DO - https://doi.org/10.1016/j.jaci.2015.10.045
M3 - Article
C2 - 26774659
SN - 0091-6749
VL - 138
SP - 107-+
JO - Journal of allergy and clinical immunology
JF - Journal of allergy and clinical immunology
IS - 1
ER -