The pharmacogenetics of asthma therapy

Asthma affects an estimated 300 million individuals worldwide, resulting in substantial morbidity, mortality, and health care utilization. The response to the three major classes of asthma therapy, beta-agonists, leukotriene antagonists, and inhaled corticosteroids, demonstrates wide inter-individual variability, with a significant number of non-responders. In addition, both asthma itself and the intermediate phenotypes of asthma that are measured in response to therapy, including the forced expiratory volume at one second (FEV1), are highly heritable. Both of these facts indicate that a significant portion of the therapeutic response to asthma may be determined by genetic factors. This review summarizes the asthma pharmacogenetics literature as it pertains to human studies, focusing on asthma pharmacogenetic phenotypes and human genetic association studies that have been published for response to each of the three major classes of asthma therapy. Of the four major classes of pharmacogenetic response, there is now evidence that genetic factors influencing the pharmacokinetics, the pharmacodynamics, and the disease modification of asthma therapies may form the basis of credible pharmacogenetic associations. Altogether, the available data indicate that an individual's likelihood of responding to a given therapy is influenced by genetics. Therefore, genetic testing may play a significant role in the care for individuals with asthma in the forseeable future.