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(Circulation. 2001;103:1608.)
© 2001 American Heart Association, Inc.

Editorials

Preprescription Genotyping

Not Yet Ready for Prime Time, but Getting There

Dan M. Roden, MD; Nancy J. Brown, MD

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

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

Key Words: Editorials • genes • drugs

There are few, if any, situations in medicine in which a clinician can predict with certainty an individual’s response to drug therapy. A host of factors can modulate this response: concomitant disease or drug therapy, sex, age, ethnicity, or dysfunction of excretory organs, to name but a few. Even when we correct for changes anticipated by such conditions, however, drug responses remain highly variable. It is an appealing concept, and one to which we subscribe, that some portion of this variability—and perhaps a great portion in many cases—is attributable to genetic factors. An increasingly sophisticated view of the genetic determinants of drug action in the context of complex diseases now raises the realistic expectation that this possibility can be addressed.

The Present Study

In this issue of Circulation, McNamara and colleagues¹ present data that a common polymorphism in the ACE gene determines response to ß-blocker therapy in ACE inhibitor–treated patients with congestive heart failure. The insertion/deletion (I/D) polymorphism in the ACE gene was first described in 1990,² and it is clear that individuals homozygous (DD) for the D allele have consistently higher ACE activity. Interestingly, despite a decade of work, the mechanism whereby the I/D polymorphism affects ACE activity is uncertain. Moreover, although the physiological consequences of the polymorphism seem clear, its actual role in mediating important diseases such as hypertension, myocardial infarction, or heart failure is not totally settled. McNamara and colleagues followed up 328 patients with heart failure and found that the prognosis was worse in patients with the DD . . . [Full Text of this Article]

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