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

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 sh...

Full description

Saved in:
Bibliographic Details
Main Authors: Malgorzata Labuda, Sophie Laberge, Julie Brière, Denis Bérubé, Patrick Beaulieu, Tomi Pastinen, Maja Krajinovic
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2011/301695
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849691911276724224
author Malgorzata Labuda
Sophie Laberge
Julie Brière
Denis Bérubé
Patrick Beaulieu
Tomi Pastinen
Maja Krajinovic
author_facet Malgorzata Labuda
Sophie Laberge
Julie Brière
Denis Bérubé
Patrick Beaulieu
Tomi Pastinen
Maja Krajinovic
author_sort Malgorzata Labuda
collection DOAJ
description 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.
format Article
id doaj-art-b3c152a6c2d04fa4a45577a95a46484a
institution DOAJ
issn 0962-9351
1466-1861
language English
publishDate 2011-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-b3c152a6c2d04fa4a45577a95a46484a2025-08-20T03:20:52ZengWileyMediators of Inflammation0962-93511466-18612011-01-01201110.1155/2011/301695301695Phosphodiesterase Type 4D Gene Polymorphism: Association with the Response to Short-Acting Bronchodilators in Paediatric Asthma PatientsMalgorzata Labuda0Sophie Laberge1Julie Brière2Denis Bérubé3Patrick Beaulieu4Tomi Pastinen5Maja Krajinovic6Research Center, CHU Sainte-Justine, Montreal, QC, H3T 1C5, CanadaDepartment of Paediatrics, University of Montreal, Montreal, Qc, H3T 1C5, CanadaResearch Center, CHU Sainte-Justine, Montreal, QC, H3T 1C5, CanadaDepartment of Paediatrics, University of Montreal, Montreal, Qc, H3T 1C5, CanadaResearch Center, CHU Sainte-Justine, Montreal, QC, H3T 1C5, CanadaDepartment of Human Genetics, McGill University and Génome Québec Innovation Centre, Montreal, Qc, H3A 1A4, CanadaResearch Center, CHU Sainte-Justine, Montreal, QC, H3T 1C5, CanadaShort-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.http://dx.doi.org/10.1155/2011/301695
spellingShingle Malgorzata Labuda
Sophie Laberge
Julie Brière
Denis Bérubé
Patrick Beaulieu
Tomi Pastinen
Maja Krajinovic
Phosphodiesterase Type 4D Gene Polymorphism: Association with the Response to Short-Acting Bronchodilators in Paediatric Asthma Patients
Mediators of Inflammation
title Phosphodiesterase Type 4D Gene Polymorphism: Association with the Response to Short-Acting Bronchodilators in Paediatric Asthma Patients
title_full Phosphodiesterase Type 4D Gene Polymorphism: Association with the Response to Short-Acting Bronchodilators in Paediatric Asthma Patients
title_fullStr Phosphodiesterase Type 4D Gene Polymorphism: Association with the Response to Short-Acting Bronchodilators in Paediatric Asthma Patients
title_full_unstemmed Phosphodiesterase Type 4D Gene Polymorphism: Association with the Response to Short-Acting Bronchodilators in Paediatric Asthma Patients
title_short Phosphodiesterase Type 4D Gene Polymorphism: Association with the Response to Short-Acting Bronchodilators in Paediatric Asthma Patients
title_sort phosphodiesterase type 4d gene polymorphism association with the response to short acting bronchodilators in paediatric asthma patients
url http://dx.doi.org/10.1155/2011/301695
work_keys_str_mv AT malgorzatalabuda phosphodiesterasetype4dgenepolymorphismassociationwiththeresponsetoshortactingbronchodilatorsinpaediatricasthmapatients
AT sophielaberge phosphodiesterasetype4dgenepolymorphismassociationwiththeresponsetoshortactingbronchodilatorsinpaediatricasthmapatients
AT juliebriere phosphodiesterasetype4dgenepolymorphismassociationwiththeresponsetoshortactingbronchodilatorsinpaediatricasthmapatients
AT denisberube phosphodiesterasetype4dgenepolymorphismassociationwiththeresponsetoshortactingbronchodilatorsinpaediatricasthmapatients
AT patrickbeaulieu phosphodiesterasetype4dgenepolymorphismassociationwiththeresponsetoshortactingbronchodilatorsinpaediatricasthmapatients
AT tomipastinen phosphodiesterasetype4dgenepolymorphismassociationwiththeresponsetoshortactingbronchodilatorsinpaediatricasthmapatients
AT majakrajinovic phosphodiesterasetype4dgenepolymorphismassociationwiththeresponsetoshortactingbronchodilatorsinpaediatricasthmapatients