Mechanisms of Pharmacogenomic Effects of Genetic Variation Within the Cardiac Adrenergic Network in Heart Failure
0026-895X/09/7603-466–480$20.00 MOLECULAR PHARMACOLOGY Vol. 76, No. 3 Copyright © 2009 The American Society for Pharmacology and Experimental Therapeutics 56572/3501253 Mol Pharmacol 76:466–480, 2009 Printed in U.S.A. MINIREVIEW Mechanisms of Pharmacogenomic Effects of Genetic Variation within the Cardiac Adrenergic Network in Heart Failure Gerald W. Dorn II and Stephen B. Liggett Center for Pharmacogenomics, Department of Internal Medicine, Washington University, St. Louis, Missouri (G.W.D.); and Downloaded from Cardiopulmonary Genomics Program, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland (S.B.L.) Received March 26, 2009; accepted June 2, 2009 ABSTRACT molpharm.aspetjournals.org One of the goals of pharmacogenomics is the use of genetic ology of the disease. Here we discuss polymorphisms within variants to predict an individual’s response to treatment. Al- the adrenergic receptor network in the context of heart failure though numerous candidate and genome-wide associations and -adrenergic receptor blocker therapy, where multiple ap- have been made for cardiovascular response-outcomes, little is proaches to understand the mechanism have been undertaken. known about how a given polymorphism imposes the pheno- We propose a comprehensive series of studies, ranging from type. Such mechanisms are important, because they tie the transfected cells, transgenic mice, and ex vivo and in vitro observed human response to specific signaling alterations and human studies as a model approach to explore mechanisms of thus provide cause-and-effect relationships, aid in the design action of pharmacogenomic effects and extend the field be- of hypothesis-based clinical studies, can help to devise work- yond observational associations.
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