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

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• 作者：Steve Turner ; MD^a ; ^{s.w.turner@abdn.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Ben Francis ; PhD^b ; Susanne Vijverberg ; PhD^c ; Maria Pino-Yanes ; PhD^d ; ^e ; Anke H. Maitland-van der Zee ; PhD^c ; Kaninika Basu ; MD^f ; Lauren Bignell ; MBBS^f ; Somnath Mukhopadhyay ; MD^f ; ^g ; Roger Tavendale ; PhD^g ; Colin Palmer ; PhD^g ; Daniel Hawcutt ; PhD^h ; Munir Pirmohamed ; PhDⁱ ; Esteban G. Burchard ; MD ; MPH^j ; ^k ; Brian Lipworth ; MD^l ; on behalf of the Pharmacogenomics in Childhood Asthma Consortium
• 关键词：Adrenergic receptors ; asthma ; child ; disease exacerbation ; therapeutics
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：138
• 期：1
• 页码：107-113.e5
• 全文大小：192 K

文摘

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

para0015">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

para0020">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

para0025">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

para0030">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.