Mechanisms of pharmacogenomic effects of genetic variation within the cardiac adrenergic network in heart failure

Gerald W. Dorn, Stephen B. Liggett

Research output: Contribution to journalShort surveypeer-review

38 Scopus citations

Abstract

One of the goals of pharmacogenomics is the use of genetic variants to predict an individual's response to treatment. Although numerous candidate and genome-wide associations have been made for cardiovascular response-outcomes, little is known about how a given polymorphism imposes the phenotype. Such mechanisms are important, because they tie the observed human response to specific signaling alterations and thus provide cause-and-effect relationships, aid in the design of hypothesis-based clinical studies, can help to devise work-around drugs, and can reveal new aspects of the pathophysiology of the disease. Here we discuss polymorphisms within the adrenergic receptor network in the context of heart failure and β-adrenergic receptor blocker therapy, where multiple approaches to understand the mechanism have been undertaken. We propose a comprehensive series of studies, ranging from transfected cells, transgenic mice, and ex vivo and in vitro human studies as a model approach to explore mechanisms of action of pharmacogenomic effects and extend the field beyond observational associations.

Original languageEnglish
Pages (from-to)466-480
Number of pages15
JournalMolecular pharmacology
Volume76
Issue number3
DOIs
StatePublished - Sep 2009

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