Variable therapeutic response in asthma: a genetic perspective

Asthma is a complex clinical syndrome with multiple genetic and environmental factors contributing to its phenotypic expression. This etiological heterogeneity adds to the complexity when addressing variation in the response to antiasthma treatment. There is regular progress in the field of asthma pharmacogenetics in determining the efficacy and potential for adverse effects of the asthma medication from a patient's genetic background. This reveals that a clinically relevant variability in response to the asthma medications may be due to genetic determinants, and refers to the polymorphisms in the genes encoding either the drug targets, or the molecular component of the downstream signal transduction pathways responsible for drug actions. The major classes of asthma therapy, β-agonists, leukotriene antagonists and inhaled corticosteroids, demonstrate wide interindividual variability. The statistical issues, such as population stratification, sample size and statistical power, are crucial factors for the identification of significant biological marker(s) for patient's response. The aim of this review is to discuss the scientific rationale and outline the genetic impact on the variability in response to different asthma medications. In conclusion, despite of new developments and recent studies in asthma pharmacogenetics, significant gaps in knowledge still remain, and several replicate studies are needed in different populations to derive firm conclusions that may help to bring pharmacotyping into clinical practice.