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(Circulation. 2003;108:3071-3074.)
© 2003 American Heart Association, Inc.

Clinician Update

Cardiovascular Pharmacogenomics

Dan M. Roden, MD

From the Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.

Correspondence to Dan M. Roden, MD, Professor of Medicine and Pharmacology and Director of the Division of Clinical Pharmacology, Vanderbilt University School of Medicine, 532 Medical Research Building I, Nashville, TN 37232. E-mail dan.roden@vanderbilt.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 

Case 1: Warfarin therapy (5 mg per day) is started in a patient with deep venous thrombosis. One week later, the patient presents with an intracerebral hemorrhage, and the INR is 11.

Case 2: Sotalol therapy is begun in a 78-year-old man with paroxysmal atrial fibrillation and heart failure. Two days later, after an episode of syncope, the patient is found to be in sinus rhythm with a QT interval of 0.7 seconds. Short runs of torsades de pointes are documented.

Case 3: Lisinopril therapy is started in a 46-year-old African-American man with a blood pressure of 170/120. The blood pressure is unchanged 1 week later.

Background: Definitions
As these cases illustrate, variability in response to drug therapy is a rule by which clinicians live. The notion that genetic factors might contribute to this variability was proposed at the beginning of the twentieth century, and the earliest examples of genetically determined aberrant drug effects were highly unusual responses in individual patients, stemming from dysfunction of a single gene product, and thus defining the field of pharmacogenetics.^1,2 Although the concepts that have evolved from these initial discoveries have considerable appeal, obstacles must be overcome before they are incorporated into clinical practice.

Contemporary basic and clinical pharmacology have evolved an increasingly sophisticated molecular view of the mechanisms underlying drug action. At the same time, literally millions of variants are being identified in genes that, by their normal function, determine these mechanisms. Some variants, termed mutations, are associated with familiar (albeit rare) diseases, such . . . [Full Text of this Article]

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