Off tempo  pg. 5

Roden has pursued the idea that there are genetic contributors to variability in drug response—“pharmacogenomics”—for most of his career, and last year he was named assistant vice chancellor for Personalized Medicine at Vanderbilt. He leads the Pharmacogenomics of Arrhythmia Therapy project, part of the Pharmacogenetics Research Network, a national effort to understand the genetics of drug responses supported by the National Institute of General Medical Sciences. Roden’s arrhythmia-focused team is poised to screen DNA samples from patients who have experienced drug-induced arrhythmias.

“The idea (of personalized medicine) has gone from an intellectual curiosity kind of thing to the notion that it may one day be possible to have generalized genetic profiles of every patient and the informatics infrastructure that will allow you to interrogate that genetic information,” Roden says.

Dan Roden, M.D.
Photo by Dean Dixon
A recent example from Darbar and Roden’s studies demonstrates how genotype might be used to tailor antiarrhythmic therapy. The team found that patients with atrial fibrillation who carry a common variation in the angiotensin-converting enzyme (ACE) gene were more likely to respond to a certain antiarrhythmic medication than patients who did not carry the variant.

“We could predict, based on genotype at one marker, how a patient will respond to the medication,” Darbar says. “This is the first example I know of a pharmacogenetic effect in atrial fibrillation.”

“In all of these spheres—arrhythmia management, drug-induced arrhythmias, sudden death,” Roden says, “the mantra is: knowing what the genetic variants are will make us smarter in terms of predicting who is at risk or not, and in terms of tailoring therapy with available drugs or tailoring new therapies.”

A tall order, perhaps, but one for which these investigators are game.

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