Pharmacogenetic and pharmacogenomic considerations of asthma treatment

ABSTRACT

Introduction: Pharmacogenetic and pharmacogenomic approaches are already utilized in some areas, such as oncology and cardiovascular disease, for selecting appropriate patients and/or establishing treatment and dosing guidelines. This is not true in asthma although many patients have different responses to drug treatment due to genetic factors.

Areas covered: Several genetic factors that affect the pharmacotherapeutic responses to asthma medications, such as β₂-AR agonists, corticosteroids, and leukotriene modifiers and could contribute to significant between-person variability in response are described.

Expert opinion: An expanding number of genetic loci have been associated with therapeutic responses to asthma drugs but the individual effect of one single-nucleotide polymorphism is partial. In fact, epigenetic changes can modify genetic effects in time-, environment-, and tissue-specific manners, genes interact together in networks, and nongenetic components such as environmental exposures, gender, nutrients, and lifestyle can significantly interact with genetics to determine the response to therapy. Therefore, well-designed randomized controlled trials or observational studies are now mandatory to define if response to asthma medications in individual patients can be improved by using pharmacogenetic predictors of treatment response. Meanwhile, routine implementation of pharmacogenetics and pharmacogenomics into clinical practice remains a futuristic, far-off challenge for many clinical practices.

KEYWORDS:

• Asthma
• pharmacogenetics
• pharmacogenomics
• β₂-adrenoceptor agonists
• inhaled corticosteroids
• leukotriene modifiers

Article highlights

• It has been suggested that 60-80% of asthma patients have different pharmacotherapeutic responses due to genetic factors.

• Pharmacogenetics and pharmacogenomics is the branch of pharmacology that specifically addresses genetic contribution to individual variability in drug therapy.

• The application of pharmacogenetics and pharmacogenomics to currently marketed drugs as a method to predict safety and efficacy is of significant value to patients, physicians, regulators, payers and industry. Pharmacogenetics and pharmacogenomics testing supports personalised medicine by translating genome-based knowledge into clinical practice, offering enhanced benefit for patients and health-care systems at large.

• An expanding number of genetic loci have been associated with therapeutic responses to asthma drugs. Heterogeneity in asthmatic patient response to the common classes of asthma therapy such as β₂-AR agonists, corticosteroids, and leukotriene modifiers, has been reported from various studies. However, many of the pharmacogenomic associations detected in large populations have only small effects on the therapeutic response.

• The individual effect of one single-nucleotide polymorphism is partial. In fact, epigenetic changes can modify genetic effects in time-, environment-, and tissue-specific manners, genes interact together in networks, and nongenetic components such as environmental exposures, gender, nutrients, and lifestyle can significantly interact with genetics to determine the response to therapy.

• Well-designed randomized controlled trials or observational studies are now mandatory to define if response to asthma medications in individual patients can be improved by using pharmacogenetic predictors of treatment response

• The routine implementation of pharmacogenetics and pharmacogenomics into clinical practice in asthma remains a futuristic, far-off challenge for many clinical practices.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper is not funded