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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 15, 2003; DOI: 10.1124/jpet.103.054569


0022-3565/03/3073-831-838$20.00
JPET 307:831-838, 2003
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PERSPECTIVES IN PHARMACOLOGY

Pharmacogenetic Considerations in Diseases of Cardiac Ion Channels

Arun Anantharam, Steven M. Markowitz, and Geoffrey W. Abbott

Division of Cardiology, Department of Medicine (A.A., S.M.M., G.W.A.); Graduate Program in Neuroscience (A.A.); Department of Pharmacology (G.W.A.); Weill Medical College of Cornell University, New York, New York

Phenotypic variation within a species arises from differences in genetic makeup between individuals. This inherent diversity empowers the species as a whole to explore and expand into new environmental niches and also to survive new stressors within an ever-changing environment. Paradoxically, one class of stressors currently challenging the human population is therapeutic drugs: medications designed to combat disease are often associated with a host of nonspecific side effects. Following earlier studies of the involvement of some cardiac ion currents in unwanted drug interactions, recent reports have identified not only the ion channel subunits involved but also a range of mutations and single nucleotide polymorphisms in ion channel genes that predispose to both drug-induced and familial cardiac arrhythmia. The tendency for individuals harboring specific, often common, gene variants to succumb to life-threatening cardiac arrhythmia, and the contribution of other factors such as drug interaction to disease etiology in these cases, are discussed here together with potential pharmacogenetic strategies for arrhythmia circumvention and therapy.


Received for publication August 5, 2003
Accepted September 2, 2003.

Address correspondence to: Dr. Geoffrey W. Abbott, Division of Cardiology, Dept. of Medicine, Weill Medical College of Cornell University, Starr 463, 520 East 70th Street, New York, NY 10021. E-mail: gwa2001{at}med.cornell.edu




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