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Mediators of Inflammation
Volume 2011, Article ID 301695, 6 pages
http://dx.doi.org/10.1155/2011/301695
Clinical Study

Phosphodiesterase Type 4D Gene Polymorphism: Association with the Response to Short-Acting Bronchodilators in Paediatric Asthma Patients

1Research Center, CHU Sainte-Justine, Montreal, QC, Canada H3T 1C5
2Department of Paediatrics, University of Montreal, Montreal, Qc, Canada H3T 1C5
3Department of Human Genetics, McGill University and Génome Québec Innovation Centre, Montreal, Qc, Canada H3A 1A4
4Department of Pharmacology, University of Montreal, Montreal, Qc, Canada H3T 1J4

Received 27 January 2011; Revised 16 June 2011; Accepted 1 July 2011

Academic Editor: E. Moilanen

Copyright © 2011 Malgorzata Labuda et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Short-acting b2-adrenergic receptor agonists are commonly used bronchodilators for symptom relief in asthmatics. The aim of this study was to test whether genetic variants in PDE4D gene, a key regulator of b2-adrenoceptor-induced cAMP turnover in airway smooth muscle cells, affect the response to short-acting b2-agonists. Bronchodilator responsiveness was assessed in 133 asthmatic children by % change in baseline forced expiratory volume in one second (FEV1) after administration of albuterol. The analyses were performed in patients with airway obstruction (FEV1/FVC ratio below 90%, n=93). FEV1  % change adjusted for baseline FEV1 values was significantly different between genotypes of rs1544791 G/A polymorphism (P=0.006) and −1345 C/T (rs1504982) promoter variation (P=0.03). The association remained significant with inclusion of age, sex, atopy, and controller medication into multivariate model (P=0.004 and P=0.02, resp.). Our work identifies new genetic variants implicated in modulation of asthma treatment, one of them (rs1544791) previously associated with asthma phenotype.