Pharmacogenetics of asthma therapy.
Asthma is a chronic disorder causing inflammation and reversible airway obstruction that affects approximately 300 million individuals worldwide. The incidence of asthma has nearly doubled in the past three decades resulting in higher rates of morbidity, mortality and health care costs. Despite the availability of several classes of asthma medications such as beta-agonists, leukotriene modifiers and corticosteroids, up to 50% of asthmatics do not benefit from one or more of these drugs. Studies have shown that asthma and drug response phenotypes such as forced expiratory volume in one second (FEV(1)) are heritable traits, indicating a genetic component of variable response to asthma drugs. This review summarizes the findings of pharmacogenetic investigations on the three main classes of asthma medications. In addition, the limitations of these genetic studies are discussed and future research avenues are proposed to identify novel genetic factors. Although numerous genes have been associated with variable response to common asthma drugs, results are often contradictory across different studies, and remain to be confirmed in larger replication cohorts. Nevertheless, literature in asthma pharmacogenetics demonstrates that genetic variants influence response to asthma treatments and may be used for predictive testing prior to drug administration to avoid adverse reactions and increase drug efficacy.
Duan
Qing Ling
QL
Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. reqdu@channing.harvard.edu
Tantisira
Kelan G
KG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000235:genetics; D014644:Genetic Variation; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D010597:Pharmacogenetics; D010641:Phenotype
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D020024:Leukotriene Antagonists