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Do genetic polymorphisms alter patient response to inhaled bronchodilators?
1Center for Pharmacogenomics and Translational Research, Nemours Children's Clinic , 807 Children's Way, Jacksonville, FL 32207 , USA , +1 904 697 3683 ; +1 904 687 7988 ; jlima@nemours.org.
Expert Opinion on Drug Metabolism & Toxicology
|August 8, 2014
Summary
Genetic variations significantly impact how individuals respond to asthma medications like short-acting and long-acting beta agonists. Pharmacogenomic studies show these genetic differences are key to understanding bronchodilator response heterogeneity.
Area of Science:
- Pharmacogenomics
- Asthma Therapeutics
- Genetic Epidemiology
Background:
- Short- and long-acting beta agonists (SABA, LABA) are standard bronchodilators for asthma.
- Bronchodilator response (BDR) exhibits significant heterogeneity, partly due to genetic factors.
- Heritability estimates suggest genetics account for 28.5% of BDR variability.
Purpose of the Study:
- To review the impact of genetic polymorphisms on bronchodilator response in asthma.
- To explore associations between gene variants and patient response to SABA and LABA.
Main Methods:
- Systematic MEDLINE search (1990-2014) using keywords: bronchodilator, ADRB2, asthma, pharmacogenomics.
- Analysis of studies investigating ADRB2 variants and their effect on BDR.
- Inclusion of single and candidate gene studies identifying other relevant genetic variants.
Main Results:
- Equivocal results exist regarding ADRB2 variants' effects on BDR and safety of SABA/LABA.
- Studies identified variants in other genes that modify bronchodilator response.
- Rare ADRB2 polymorphisms (Thr164Ile, -376 indel) linked to hospital admissions and life-threatening events with LABA.
Conclusions:
- Pharmacogenomic research over two decades confirms that genetic polymorphisms influence patient response to bronchodilators in asthma.
- Understanding these genetic factors is crucial for personalized asthma treatment strategies.
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