Arg16 ADRB2 genotype increases the risk of asthma exacerbation in children with a reported use of long-acting β2-agonists: results of the pacman cohort

Author:

Zuurhout Miranda JL1,Vijverberg Susanne JH12,Raaijmakers Jan AM1,Koenderman Leo2,Postma Dirkje S3,Koppelman Gerard H4,Maitland-van der Zee Anke Hilse5

Affiliation:

1. Utrecht University, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherland>

2. University Medical Center Utrecht, Department of Respiratory Medicine, Utrecht, The Netherlands

3. University of Groningen, University Medical Center Groningen, Department of Pulmonology, GRIAC Research Institute for Asthma & COPD, Groningen, The Netherland

4. University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Department of Paediatric Pulmonology & Paediatric Allergology, GRIAC Research Institute for Asthma & COPD, Groningen, The Netherland

5. Utrecht University, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherland.

Abstract

Background: Current evidence suggests that asthma patients with the ADRB2 Arg16 genotype have a poorer response to long-acting β2-agonists (LABA), but the results remain inconsistent. Aim: This study assessed the association between Arg16 variants and treatment outcome in children treated with inhaled corticosteroids (ICS) and LABA. Materials & methods: ADRB2 Arg16 was genotyped in 597 children (4–12 years of age) participating in the PACMAN cohort study. A questionnaire was used to assess asthma control, frequency of asthma-related emergency department visits and use of oral corticosteroids in the past year. Results: Arg/Arg carriers with a reported use of ICS and LABA had an increased risk of oral corticosteroid use (odds ratio: 14.9; 95% CI: 1.59–140.1) and emergency department visits in the past year (odds ratio: 11.9; 95% CI: 1.22–115.8) compared to Gly/Gly carriers. This effect was not observed in Arg/Arg genotype carriers reporting ICS use only. Conclusion: Children who are homozygous for ADRB2 Arg16 have an increased risk of exacerbations when treated with combined LABA and ICS. Original submitted 4 September 2013; Revision submitted 27 September 2013

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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