Pharmacogenetics of asthma.
OBJECTIVE
Patient response to the asthma drug classes, bronchodilators, inhaled corticosteroids and leukotriene modifiers, are characterized by a large degree of heterogeneity, which is attributable in part to genetic variation. Herein, we review and update the pharmacogenetics and pharmaogenomics of common asthma drugs.


RESULTS
Early studies suggest that bronchodilator reversibility and asthma worsening in patients on continuous short-acting and long-acting beta-agonists are related to the Gly16Arg genotype for the ADRB2. More recent studies including genome-wide association studies implicate variants in other genes contribute to bronchodilator response heterogeneity and fail to replicate asthma worsening associated with continuous beta-agonist use. Genetic determinants of the safety of long-acting beta-agonist require further study. Variants in CRHR1, TBX21, and FCER2 contribute to variability in response for lung function, airways responsiveness, and exacerbations in patients taking inhaled corticosteroids. Variants in ALOX5, LTA4H, LTC4S, ABCC1, CYSLTR2, and SLCO2B1 contribute to variability in response to leukotriene modifiers.


CONCLUSIONS
Identification of novel variants that contribute to response heterogeneity supports future studies of single nucleotide polymorphism discovery and include gene expression and genome-wide association studies. Statistical models that predict the genomics of response to asthma drugs will complement single nucleotide polymorphism discovery in moving toward personalized medicine.
Lima
John J
JJ
Centers for Pediatric Clinical Pharmacology and Pharmacogenetics, Nemours Children's Clinic, Jacksonville, Florida 32207, USA. Jlima@nemours.org
Blake
Kathryn V
KV
Tantisira
Kelan G
KG
Weiss
Scott T
ST
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D020024:Leukotriene Antagonists