Overview of the pharmacogenetics of asthma treatment.
Asthma affects approximately 300 million individuals worldwide. Medications comprise a substantial portion of asthma expenditures. Despite the availability of three primary therapeutic classes of medications, there are a significant number of nonresponders to therapy. Available data, as well as previous pharmacogenetic studies, suggest that genetics may contribute as much as 60-80% to the interindividual variability in treatment response. In this methodologic review, after providing a broad overview of the asthma pharmacogenetics literature to date, we describe the application of a novel family-based screening algorithm to the analysis of pharmacogenetic data and highlight our approach to identifying and verifying loci influencing asthma treatment response. This approach seeks to address issues related to multiple comparisons, statistical power, population stratification, and failure to replicate from which previous population-based or case-control pharmacogenetic association studies may suffer. Identification of such replicable loci is the next step towards the goal of 'individualized therapy' for asthma.
Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA.
S T
ST
Weiss
A A
AA
Litonjua
C
C
Lange
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R
Lazarus
S B
SB
Liggett
E R
ER
Bleecker
K G
KG
Tantisira
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000465:Algorithms; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D000099052:CRF Receptor, Type 1
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D020024:Leukotriene Antagonists; D011943:Receptors, Adrenergic, beta; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D001094:Arachidonate 5-Lipoxygenase