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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

Impact of genetic variants in human disease.Notes: Multiple common genetic variants with small to modest effect sizes contribute to common disease susceptibility and therapeutic responsiveness in an additive fashion. Genome-wide association studies have identified common variants associated with risk for asthma, response to short-acting beta agonists, and response to inhaled corticosteroids. In contrast, rare genetic variants contribute to susceptibility for common diseases and, potentially, response to pharmacologic therapies with a large effect size. Adapted from Tsuji S. Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum Mol Genet. 2010;19(R1):R65–R70.84
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f3-pgpm-8-009: Impact of genetic variants in human disease.Notes: Multiple common genetic variants with small to modest effect sizes contribute to common disease susceptibility and therapeutic responsiveness in an additive fashion. Genome-wide association studies have identified common variants associated with risk for asthma, response to short-acting beta agonists, and response to inhaled corticosteroids. In contrast, rare genetic variants contribute to susceptibility for common diseases and, potentially, response to pharmacologic therapies with a large effect size. Adapted from Tsuji S. Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum Mol Genet. 2010;19(R1):R65–R70.84

Mentions: A common ADRB2 variant, such as Gly16Arg, has an allele frequency of 40%–50% in ethnic groups from the USA; however, other racial groups may have a higher frequency of the Arg16 allele, including Asian populations. Thus, Gly16Arg likely has a small effect on LABA responsiveness and it is more likely that a rare variant with a strong biologic effect could account for the uncommon, severe adverse responses observed in less than 1% of the subjects randomized to LABA in the SMART cohort (Figure 3). Resequencing of ADRB2 in multi-ethnic asthma populations has identified different rare variants with a frequency of less than 5%, most of which were unique to a particular ethnic group.45,46 For instance, Thr164Ile is a rare coding variant, more common in non-Hispanic whites, while a 24-base-pair promoter insertion variant at nucleotide position −376 relative to the start codon (ie, −376 In-Del) was only identified in African Americans and Puerto Ricans.45–47


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

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

Impact of genetic variants in human disease.Notes: Multiple common genetic variants with small to modest effect sizes contribute to common disease susceptibility and therapeutic responsiveness in an additive fashion. Genome-wide association studies have identified common variants associated with risk for asthma, response to short-acting beta agonists, and response to inhaled corticosteroids. In contrast, rare genetic variants contribute to susceptibility for common diseases and, potentially, response to pharmacologic therapies with a large effect size. Adapted from Tsuji S. Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum Mol Genet. 2010;19(R1):R65–R70.84
© Copyright Policy
Related In: Results  -  Collection

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

f3-pgpm-8-009: Impact of genetic variants in human disease.Notes: Multiple common genetic variants with small to modest effect sizes contribute to common disease susceptibility and therapeutic responsiveness in an additive fashion. Genome-wide association studies have identified common variants associated with risk for asthma, response to short-acting beta agonists, and response to inhaled corticosteroids. In contrast, rare genetic variants contribute to susceptibility for common diseases and, potentially, response to pharmacologic therapies with a large effect size. Adapted from Tsuji S. Genetics of neurodegenerative diseases: insights from high-throughput resequencing. Hum Mol Genet. 2010;19(R1):R65–R70.84
Mentions: A common ADRB2 variant, such as Gly16Arg, has an allele frequency of 40%–50% in ethnic groups from the USA; however, other racial groups may have a higher frequency of the Arg16 allele, including Asian populations. Thus, Gly16Arg likely has a small effect on LABA responsiveness and it is more likely that a rare variant with a strong biologic effect could account for the uncommon, severe adverse responses observed in less than 1% of the subjects randomized to LABA in the SMART cohort (Figure 3). Resequencing of ADRB2 in multi-ethnic asthma populations has identified different rare variants with a frequency of less than 5%, most of which were unique to a particular ethnic group.45,46 For instance, Thr164Ile is a rare coding variant, more common in non-Hispanic whites, while a 24-base-pair promoter insertion variant at nucleotide position −376 relative to the start codon (ie, −376 In-Del) was only identified in African Americans and Puerto Ricans.45–47

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