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Pharmacogenetics of Bronchodilator Response: Future Directions

Current Allergy and Asthma Reports volume 21, Article number: 47 (2021) Cite this article

Abstract

Purpose of Review

Several genome-wide association studies (GWASs) of bronchodilator response (BDR) to albuterol have been published over the past decade. This review describes current knowledge gaps, including pharmacogenetic studies of albuterol response in minority populations, effect modification of pharmacogenetic associations by age, and relevance of BDR phenotype characterization to pharmacogenetic findings. New approaches, such as leveraging additional “omics” data to focus pharmacogenetic interrogation, as well as developing polygenic risk scores in asthma treatment responses, are also discussed.

Recent Findings

Recent pharmacogenetic studies of albuterol response in minority populations have identified genetic polymorphisms in loci (DNAH5, NFKB1, PLCB1, ADAMTS3, COX18, and PRKG1), that are associated with BDR. Additional studies are needed to replicate these findings. Modification of the pharmacogenetic associations for SPATS2L and ASB3 polymorphisms by age has also been published. Evidence from metabolomic and epigenomic studies of BDR may point to new pharmacogenetic targets. Lastly, a polygenic risk score for response to albuterol has been developed but requires validation in additional cohorts.

Summary

In order to expand our knowledge of pharmacogenetics of BDR, additional studies in minority populations are needed. Consideration of effect modification by age and leverage of other “omics” data beyond genomics may also help uncover novel pharmacogenetic loci for use in precision medicine for asthma treatment.

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Funding

This work was funded by National Institutes of Health (NIH) grants: R01HD085993 and K01HL125858.

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Authors and Affiliations

  1. PrecisiOn Medicine Translational Research (PROMoTeR) Center, Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care, MA, Boston, USA

    Joanne E. Sordillo, Sharon M. Lutz & Ann Chen Wu

  2. Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Rachel S. Kelly & Jessica Lasky-Su

Authors
  1. Joanne E. Sordillo
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  2. Rachel S. Kelly
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Corresponding author

Correspondence to Ann Chen Wu.

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Conflict of Interest

Joanne Sordillo, Sharon Lutz, Jessica Lasky-Su, and Rachel Kelly declare that they have no conflict of interest. Ann Chen Wu reports grants from GlaxoSmithKline, outside the submitted work.

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All reported studies/experiments with human subjects mentioned in this review that were performed by the authors were performed in accordance with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines.

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Sordillo, J.E., Kelly, R.S., Lutz, S.M. et al. Pharmacogenetics of Bronchodilator Response: Future Directions. Curr Allergy Asthma Rep 21, 47 (2021). https://doi.org/10.1007/s11882-021-01023-w

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  • DOI: https://doi.org/10.1007/s11882-021-01023-w

Keywords

  • Bronchodilator response
  • Pharmacogenetics
  • β2-agonist
  • Polygenic risk score
  • Effect modification by age