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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

Two rare ADRB2 variants and asthma-related hospitalization with LABA treatment.Notes: Thr164Ile is shown in (A) and a 25 base-pair insertion-deletion at position −376 in relation to the start codon (−376 In-Del) is shown in (B). Reprinted from Lancet Respir Med. 2014;2(3). Ortega VE, Hawkins GA, Moore WC, et al. Effect of rare genetic variants in ADRB2 on risk of severe exacerbations and symptom control during longacting beta agonist treatment in a multiethnic asthma population. 204–213. Copyright © 2014 with permission from Elsevier.46Abbreviations: LABA, long-acting beta agonist; CI, confidence interval; OR, odds ratio.
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f4-pgpm-8-009: Two rare ADRB2 variants and asthma-related hospitalization with LABA treatment.Notes: Thr164Ile is shown in (A) and a 25 base-pair insertion-deletion at position −376 in relation to the start codon (−376 In-Del) is shown in (B). Reprinted from Lancet Respir Med. 2014;2(3). Ortega VE, Hawkins GA, Moore WC, et al. Effect of rare genetic variants in ADRB2 on risk of severe exacerbations and symptom control during longacting beta agonist treatment in a multiethnic asthma population. 204–213. Copyright © 2014 with permission from Elsevier.46Abbreviations: LABA, long-acting beta agonist; CI, confidence interval; OR, odds ratio.

Mentions: In a recent pharmacogenetic study of rare ADRB2 variants, the rare Thr164Ile and −376 In-Del variants were associated with asthma-related hospitalization in the past year in non-Hispanic white and African American asthmatics treated with a LABA, respectively (Figure 4A and B). Each rare ADRB2 variant was also associated with asthma-related urgent outpatient visits and a requirement for regular systemic glucocorticoid use in LABA-treated subjects from each ethnic group. This increased risk of severe exacerbations and poor symptom control was only observed in LABA-treated asthmatic subjects in each ethnic group, suggesting a gene-by-environment interaction for these two rare ADRB2 variants (Figure 4A and B).46 These rare variants are an example of the importance of considering different rare variants unique to different ethnic groups in pharmacogenetic studies. Thus, rare variants such as those in ADRB2 are potential biomarkers for more personalized, precise, guideline-based treatment strategies in the small subgroup of asthmatics with altered responsiveness to LABA and ICS combination therapy.


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

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

Two rare ADRB2 variants and asthma-related hospitalization with LABA treatment.Notes: Thr164Ile is shown in (A) and a 25 base-pair insertion-deletion at position −376 in relation to the start codon (−376 In-Del) is shown in (B). Reprinted from Lancet Respir Med. 2014;2(3). Ortega VE, Hawkins GA, Moore WC, et al. Effect of rare genetic variants in ADRB2 on risk of severe exacerbations and symptom control during longacting beta agonist treatment in a multiethnic asthma population. 204–213. Copyright © 2014 with permission from Elsevier.46Abbreviations: LABA, long-acting beta agonist; CI, confidence interval; OR, odds ratio.
© Copyright Policy
Related In: Results  -  Collection

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

f4-pgpm-8-009: Two rare ADRB2 variants and asthma-related hospitalization with LABA treatment.Notes: Thr164Ile is shown in (A) and a 25 base-pair insertion-deletion at position −376 in relation to the start codon (−376 In-Del) is shown in (B). Reprinted from Lancet Respir Med. 2014;2(3). Ortega VE, Hawkins GA, Moore WC, et al. Effect of rare genetic variants in ADRB2 on risk of severe exacerbations and symptom control during longacting beta agonist treatment in a multiethnic asthma population. 204–213. Copyright © 2014 with permission from Elsevier.46Abbreviations: LABA, long-acting beta agonist; CI, confidence interval; OR, odds ratio.
Mentions: In a recent pharmacogenetic study of rare ADRB2 variants, the rare Thr164Ile and −376 In-Del variants were associated with asthma-related hospitalization in the past year in non-Hispanic white and African American asthmatics treated with a LABA, respectively (Figure 4A and B). Each rare ADRB2 variant was also associated with asthma-related urgent outpatient visits and a requirement for regular systemic glucocorticoid use in LABA-treated subjects from each ethnic group. This increased risk of severe exacerbations and poor symptom control was only observed in LABA-treated asthmatic subjects in each ethnic group, suggesting a gene-by-environment interaction for these two rare ADRB2 variants (Figure 4A and B).46 These rare variants are an example of the importance of considering different rare variants unique to different ethnic groups in pharmacogenetic studies. Thus, rare variants such as those in ADRB2 are potential biomarkers for more personalized, precise, guideline-based treatment strategies in the small subgroup of asthmatics with altered responsiveness to LABA and ICS combination therapy.

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