Phosphodiesterase type 4D gene polymorphism: association with the response to short-acting bronchodilators in paediatric asthma patients

Mediators Inflamm. 2011;2011:301695. doi: 10.1155/2011/301695. Epub 2011 Aug 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Agonists / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / enzymology*
  • Bronchodilator Agents / pharmacology
  • Bronchodilator Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
  • Forced Expiratory Volume / drug effects
  • Humans
  • Polymorphism, Genetic*
  • Respiratory Function Tests
  • Vital Capacity / drug effects


  • Adrenergic beta-Agonists
  • Bronchodilator Agents
  • Cyclic Nucleotide Phosphodiesterases, Type 4