title: Phosphodiesterase type 4D gene polymorphism: association with the response to short-acting bronchodilators in paediatric asthma patients.
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 (FEV(1)) after administration of albuterol. The analyses were performed in patients with airway obstruction (FEV(1)/FVC ratio below 90%, n = 93). FEV(1)  % change adjusted for baseline FEV(1) 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.
authors.affiliation: Research Center, CHU Sainte-Justine, Montreal, QC, Canada.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Labuda
authors.forename: Sophie
authors.initials: S
authors.lastname: Laberge
authors.forename: Julie
authors.initials: J
authors.lastname: Brière
authors.forename: Denis
authors.initials: D
authors.lastname: Bérubé
authors.forename: Patrick
authors.initials: P
authors.lastname: Beaulieu
authors.forename: Tomi
authors.initials: T
authors.lastname: Pastinen
authors.forename: Maja
authors.initials: M
authors.lastname: Krajinovic
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology*; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics* / Q000378:metabolism; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4