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Asthma pharmacogenetics and the development of genetic profiles for personalized medicine.

Ortega VE, Meyers DA, Bleecker ER - Pharmgenomics Pers Med (2015)

Bottom Line: Genetic profiles will consist of gene variants that predict individual disease susceptibility and risk for progression, predict which pharmacologic therapies will result in a maximal therapeutic benefit, and predict whether a therapy will result in an adverse response and should be avoided in a given individual.Pharmacogenetic studies of the glucocorticoid, leukotriene, and β2-adrenergic receptor pathways have focused on candidate genes within these pathways and, in addition to a small number of genome-wide association studies, have identified genetic loci associated with therapeutic responsiveness.The benefit of a personalized, tailored approach to health care delivery is needed in the development of expensive biologic drugs directed at a specific biologic pathway.

View Article: PubMed Central - PubMed

Affiliation: Center for Genomics and Personalized Medicine Research, Pulmonary Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.

ABSTRACT
Human genetics research will be critical to the development of genetic profiles for personalized or precision medicine in asthma. Genetic profiles will consist of gene variants that predict individual disease susceptibility and risk for progression, predict which pharmacologic therapies will result in a maximal therapeutic benefit, and predict whether a therapy will result in an adverse response and should be avoided in a given individual. Pharmacogenetic studies of the glucocorticoid, leukotriene, and β2-adrenergic receptor pathways have focused on candidate genes within these pathways and, in addition to a small number of genome-wide association studies, have identified genetic loci associated with therapeutic responsiveness. This review summarizes these pharmacogenetic discoveries and the future of genetic profiles for personalized medicine in asthma. The benefit of a personalized, tailored approach to health care delivery is needed in the development of expensive biologic drugs directed at a specific biologic pathway. Prior pharmacogenetic discoveries, in combination with additional variants identified in future studies, will form the basis for future genetic profiles for personalized tailored approaches to maximize therapeutic benefit for an individual asthmatic while minimizing the risk for adverse events.

No MeSH data available.


Related in: MedlinePlus

ACRN Beta Agonist Response by Genotype (BARGE) trial.Notes: In the BARGE trial, Arg16 homozygotes experienced no change in PEFR during albuterol treatment while Gly16 homozygotes experienced an improvement in PEFR during regular albuterol therapy. In addition, Arg16 homozygotes experienced an improvement in PEFR during placebo treatment. Reprinted from The Lancet. 2004;364(9444). Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. 1505–1512. Copyright © 2004, with permission from Elsevier.9Abbreviations: ACRN, Asthma Clinical Research Network; PEFR, peak expiratory flow rate.
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f2-pgpm-8-009: ACRN Beta Agonist Response by Genotype (BARGE) trial.Notes: In the BARGE trial, Arg16 homozygotes experienced no change in PEFR during albuterol treatment while Gly16 homozygotes experienced an improvement in PEFR during regular albuterol therapy. In addition, Arg16 homozygotes experienced an improvement in PEFR during placebo treatment. Reprinted from The Lancet. 2004;364(9444). Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. 1505–1512. Copyright © 2004, with permission from Elsevier.9Abbreviations: ACRN, Asthma Clinical Research Network; PEFR, peak expiratory flow rate.

Mentions: Subsequent pharmacogenetic studies of two independent clinical trial cohorts (on long-term lung function response to regular albuterol treatment) showed that Arg16 homozygotes experienced a decline in peak expiratory flow rate (PEFR), while PEFR remained unchanged in Gly16 homozygotes, prompting one of the first prospective genotype-stratified studies of Gly16Arg genotypes by the National Heart, Lung, and Blood Institute Asthma Clinical Research Network, ie, BARGE (Beta Agonist Response by Genotype).9,50,51 The genotype-stratified design of the BARGE trial ensured that a sufficient number of the less frequent Arg16 homozygotes were randomized to regular albuterol or placebo in this cross-over study (rescue inhaler use was primarily limited to ipratropium to minimize beta agonist exposure). In the BARGE trial, Gly16 homozygotes experienced an increase in PEFR and an improvement in asthma symptom scores and rescue inhaler use during regular albuterol therapy (Figure 2). In contrast, PEFR did not change in Arg16 homozygotes who experienced a deterioration in symptoms and increased rescue inhaler use during regular albuterol treatment (Figure 2).9


Asthma pharmacogenetics and the development of genetic profiles for personalized medicine.

Ortega VE, Meyers DA, Bleecker ER - Pharmgenomics Pers Med (2015)

ACRN Beta Agonist Response by Genotype (BARGE) trial.Notes: In the BARGE trial, Arg16 homozygotes experienced no change in PEFR during albuterol treatment while Gly16 homozygotes experienced an improvement in PEFR during regular albuterol therapy. In addition, Arg16 homozygotes experienced an improvement in PEFR during placebo treatment. Reprinted from The Lancet. 2004;364(9444). Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. 1505–1512. Copyright © 2004, with permission from Elsevier.9Abbreviations: ACRN, Asthma Clinical Research Network; PEFR, peak expiratory flow rate.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325626&req=5

f2-pgpm-8-009: ACRN Beta Agonist Response by Genotype (BARGE) trial.Notes: In the BARGE trial, Arg16 homozygotes experienced no change in PEFR during albuterol treatment while Gly16 homozygotes experienced an improvement in PEFR during regular albuterol therapy. In addition, Arg16 homozygotes experienced an improvement in PEFR during placebo treatment. Reprinted from The Lancet. 2004;364(9444). Israel E, Chinchilli VM, Ford JG, et al. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. 1505–1512. Copyright © 2004, with permission from Elsevier.9Abbreviations: ACRN, Asthma Clinical Research Network; PEFR, peak expiratory flow rate.
Mentions: Subsequent pharmacogenetic studies of two independent clinical trial cohorts (on long-term lung function response to regular albuterol treatment) showed that Arg16 homozygotes experienced a decline in peak expiratory flow rate (PEFR), while PEFR remained unchanged in Gly16 homozygotes, prompting one of the first prospective genotype-stratified studies of Gly16Arg genotypes by the National Heart, Lung, and Blood Institute Asthma Clinical Research Network, ie, BARGE (Beta Agonist Response by Genotype).9,50,51 The genotype-stratified design of the BARGE trial ensured that a sufficient number of the less frequent Arg16 homozygotes were randomized to regular albuterol or placebo in this cross-over study (rescue inhaler use was primarily limited to ipratropium to minimize beta agonist exposure). In the BARGE trial, Gly16 homozygotes experienced an increase in PEFR and an improvement in asthma symptom scores and rescue inhaler use during regular albuterol therapy (Figure 2). In contrast, PEFR did not change in Arg16 homozygotes who experienced a deterioration in symptoms and increased rescue inhaler use during regular albuterol treatment (Figure 2).9

Bottom Line: Genetic profiles will consist of gene variants that predict individual disease susceptibility and risk for progression, predict which pharmacologic therapies will result in a maximal therapeutic benefit, and predict whether a therapy will result in an adverse response and should be avoided in a given individual.Pharmacogenetic studies of the glucocorticoid, leukotriene, and β2-adrenergic receptor pathways have focused on candidate genes within these pathways and, in addition to a small number of genome-wide association studies, have identified genetic loci associated with therapeutic responsiveness.The benefit of a personalized, tailored approach to health care delivery is needed in the development of expensive biologic drugs directed at a specific biologic pathway.

View Article: PubMed Central - PubMed

Affiliation: Center for Genomics and Personalized Medicine Research, Pulmonary Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.

ABSTRACT
Human genetics research will be critical to the development of genetic profiles for personalized or precision medicine in asthma. Genetic profiles will consist of gene variants that predict individual disease susceptibility and risk for progression, predict which pharmacologic therapies will result in a maximal therapeutic benefit, and predict whether a therapy will result in an adverse response and should be avoided in a given individual. Pharmacogenetic studies of the glucocorticoid, leukotriene, and β2-adrenergic receptor pathways have focused on candidate genes within these pathways and, in addition to a small number of genome-wide association studies, have identified genetic loci associated with therapeutic responsiveness. This review summarizes these pharmacogenetic discoveries and the future of genetic profiles for personalized medicine in asthma. The benefit of a personalized, tailored approach to health care delivery is needed in the development of expensive biologic drugs directed at a specific biologic pathway. Prior pharmacogenetic discoveries, in combination with additional variants identified in future studies, will form the basis for future genetic profiles for personalized tailored approaches to maximize therapeutic benefit for an individual asthmatic while minimizing the risk for adverse events.

No MeSH data available.


Related in: MedlinePlus