Salmeterol response is not affected by β2-adrenergic receptor genotype in subjects with persistent asthma

Bleecker, Eugene R.; Yancey, Steven W.; Baitinger, Leslie; Edwards, Lisa; Klotsman, Michael; Anderson, Wayne H.; Dorinsky, Paul

doi:10.1016/j.jaci.2006.06.036

Cited by 144 publications

(92 citation statements)

References 33 publications

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“…45,[65][66][67] During regular therapy with LABA, reduced responses in Arg16 homozygotes have been reported in two small studies 69 but have not been found in several other larger studies. 65,[72][73][74] It is unclear why there are differences in pharmacogenetic responses to short and long acting beta except that they may be related to the longer duration of action of LABAs. In view of the overall safety and efficacy of LABA therapy and the lack of a therapeutic benefit of regular SABA therapy, these pharmacogenetic observations should not alter the current standard of care which encourages the use of as-needed SABA therapy or regular LABA and ICS combination therapy to achieve optimal control of asthma symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…(Figure 7) During the run-out period, all subjects exhibited a similar and predictable decline in asthma control. 72 Issues with this clinical trial include the shorter 12-week duration of the study which may not have been long enough to detect the pharmacogenetic effects reported in the SOCS and SLIC trial. However, the findings reported by Bleecker and co-workers suggest that Gly 16 Arg genotypes may not be a genetic determinant of reduced responses to chronic LABA therapy in the presence of ICS therapy.…”

Section: Adrβ2 Pharmacogenetics and The Response To Laba Therapymentioning

confidence: 99%

“…However, the findings reported by Bleecker and co-workers suggest that Gly 16 Arg genotypes may not be a genetic determinant of reduced responses to chronic LABA therapy in the presence of ICS therapy. 72 More recently there have been two reports that do not show an effect of variation at the Arg 16 Gly locus on the response to LABA Therapy. 73,74 In addition, the NHLBI ACRN network is currently investigating variation at the Arg 16 Gly locus in the Long Acting Beta Agoinst response by genotype (LARGE) study.…”

Section: Adrβ2 Pharmacogenetics and The Response To Laba Therapymentioning

confidence: 99%

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Pharmacogenetics of the β2-Adrenergic Receptor Gene

Ortega

Hawkins

Peters

et al. 2007

Immunology and Allergy Clinics of North America

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Asthma is a complex genetic disease with multiple genetic and environmental determinants contributing to the observed variability in response to common anti-asthma therapies. Asthma pharmacogenetic research has focused on multiple candidate genes including the β2-adrenergic receptor gene (ADRβ2) and its effect on individual responses to beta agonist therapy. At present, knowledge about the effects of ADRβ2 variation on therapeutic responses is evolving and should not alter current Asthma Guideline approaches consisting of the use of short acting beta agonists for as-needed symptom based therapy and the use of a regular long-acting beta agonist in combination with inhaled corticosteroid therapy for optimal control of asthma symptoms in those asthmatics who are not controlled on inhaled corticosteroid alone. This approach is based upon studies showing a consistent pharmacogenetic response to regular use of short acting beta agonists (SABA) and less consistent findings in studies evaluating long acting beta agonist (LABA). While emerging pharmacogenetic studies are provocative and should lead to functional approaches, conflicting data with responses to LABA therapy may be caused by factors that include small sample sizes of study populations and differences in experimental design that may limit the conclusions that may be drawn from these clinical trials at the present time.

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Section: Discussionmentioning

confidence: 99%

Section: Adrβ2 Pharmacogenetics and The Response To Laba Therapymentioning

confidence: 99%

Section: Adrβ2 Pharmacogenetics and The Response To Laba Therapymentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenetics of the β2-Adrenergic Receptor Gene

Ortega

Hawkins

Peters

et al. 2007

Immunology and Allergy Clinics of North America

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“…In line with the studies assessing genetic variants associated with SABA response, most pharmacogenetics studies on LABA response have focused on the ADRB2 gene. In adults, most retrospective pharmacogenetics studies showed no effect of the ADRB2 genotype on lung function improvement [21,22]. In addition, the prospective genotype stratified trial by Wechsler et al confirmed these results [23].…”

Section: Long-acting Beta-2 Agonistsmentioning

confidence: 94%

Treatment response heterogeneity in asthma: the role of genetic variation

Vijverberg

Farzan

Slob

et al. 2017

Expert Review of Respiratory Medicine

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Introduction: Asthmatic patients show a large heterogeneity in response to asthma medication. Rapidly evolving genotyping technologies have led to the identification of various genetic variants associated with treatment outcomes. Areas covered: This review focuses on the current knowledge of genetic variants influencing treatment response to the most commonly used asthma medicines: short-and long-acting beta-2 agonists (SABA/ LABA), inhaled corticosteroids (ICS) and leukotriene modifiers. This review shows that various genetic variants have been identified, but none are currently used to guide asthma treatment. One of the most promising genetic variants is the Arg16 variant in the ADRB2 gene to guide LABA treatment in asthmatic children. Expert commentary: Poor replication of initially promising results and the low fraction of variability accounted for by single genetic variants inhibit pharmacogenetic findings to reach the asthma clinic. Nevertheless, the identification of genetic variation influencing treatment response does provide more insights in the complex processes underlying response and might identify novel targets for treatment. There is a need to report measures of clinical validity, to perform precision-medicine guided trials, as well as to understand how genetic variation interacts with environmental factors. In addition, systems biology approaches might be able to show a more complete picture of these complex interactions.ARTICLE HISTORY

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“…The concerns regarding b-adrenergic receptor polymorphisms and their influence on chronic b-agonist therapy have also been evaluated in patients using long-acting b-agonists. In retrospective analyses, adverse consequences based on genotype have not been observed (32).…”

Section: Chronic B-agonist Therapymentioning

confidence: 99%

Asthma Therapies Revisited: What Have We Learned?

Lemanske

2009

Proceedings of the American Thoracic Society

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Asthma is a heterogenous disorder related to numerous biologic, immunologic, and physiologic components that generate multiple clinical phenotypes. Further, genetic and environmental factors interact in ways that produce variability in both disease onset and severity and differential expression based on both the age and sex of the patient. Thus, the natural history of asthma is complex in terms of disease expression, remission, relapse, and progression. As such, therapy for asthma is complicated and has been approached from the standpoints of primary, secondary, and tertiary prevention. Presently, asthma cannot be cured but can be controlled in most patients, an indication that most of the success clinical research strategies have realized has been in the area of tertiary prevention. Since for many adult patients with asthma their disease had its roots in early life, much recent research has focused on events during early childhood that can be linked to subsequent asthma development with the hopes of creating appropriate interventions to alter its natural history of expression. These research approaches can be categorized into three questions. Who is the right patient to treat? When is the right time to begin treatment? And finally, what is the appropriate treatment to prescribe?

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Salmeterol response is not affected by β2-adrenergic receptor genotype in subjects with persistent asthma

Cited by 144 publications

References 33 publications

Pharmacogenetics of the β2-Adrenergic Receptor Gene

Pharmacogenetics of the β2-Adrenergic Receptor Gene

Treatment response heterogeneity in asthma: the role of genetic variation

Asthma Therapies Revisited: What Have We Learned?

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