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Review
. 2011 Dec;11(6):383-92.
doi: 10.1038/tpj.2011.46. Epub 2011 Oct 11.

The pharmacogenetics and pharmacogenomics of asthma therapy

S M Tse  1 , K Tantisira, S T Weiss
Affiliations
Review

The pharmacogenetics and pharmacogenomics of asthma therapy

S M Tse et al. Pharmacogenomics J. 2011 Dec.

Abstract

Despite the availability of several classes of asthma medications and their overall effectiveness, a significant portion of patients fail to respond to these therapeutic agents. Evidence suggests that genetic factors may partly mediate the heterogeneity in asthma treatment response. This review discusses important findings in asthma pharmacogenetic and pharmacogenomic studies conducted to date, examines limitations of these studies and, finally, proposes future research directions in this field. The focus will be on the three major classes of asthma medications: β-adrenergic receptor agonists, inhaled corticosteroids and leukotriene modifiers. Although many studies are limited by small sample sizes and replication of the findings is needed, several candidate genes have been identified. High-throughput technologies are also allowing for large-scale genetic investigations. Thus, the future is promising for a personalized treatment of asthma, which will improve therapeutic outcomes, minimize side effects and lead to a more cost-effective care.

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Conflict of interest statement

Conflicts of interest

The authors declare no conflicts of interest related to this manuscript.

Figures

Figure 1
Figure 1
Distribution of the bronchodilator response across the three major asthma networks in SHARP. Note that, despite highly varying enrollment criteria, the overall distribution of response is remarkably similar between the clinical trial networks. This supports the ability to harmonize asthma pharmacogenetic phenotypes and the likely presence of common genetic determinants of response. ACRN=Asthma Clinical Research Network; CAMP=Children Asthma Management Program; CARE=Childhood Asthma Research and Education.
Figure 2
Figure 2
Polymorphisms in ADRB2. Arg16Gly and Gln27Glu are located positions +47 and +79 respectively and are shown in the transmembrane β2-adrenergic receptor.
Figure 3
Figure 3
Overview of the glucocorticoid pathway. The binding of glucocorticoid (GC) to the intracellular glucocorticoid receptor (GR) results in activation of the complex and dissociation of inhibitory proteins that usually keeps GR inactive. These include Hsp90, Hsp70 (heat shock proteins), the p23 phosphoprotein and FKBP52. The GC-GR complex translocates into the nucleus and alters transcription of genes involved in inflammation.
Figure 4
Figure 4
Overview of the leukotriene pathway, demonstrating the site of action of anti-leukotriene therapies.
See this image and copyright information in PMC

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