April 2008
A study published in the March 6 issue of the New England Journal of Medicine sheds new light on how genetic variation affects patients’ initial response to the common blood thinner warfarin (Coumadin). The finding could help doctors determine the optimal dose of warfarin more quickly and precisely through genetic screening and could reduce the incidence of side effects from the drug, particularly severe bleeding.
An estimated 2 million people in the United States take warfarin to prevent blood clots, but warfarin therapy is challenging because patients’ responses to the drug vary widely. Last year the U.S. Food and Drug Administration (FDA) approved updated labeling for warfarin to notify doctors that genetic testing could help improve their estimates for the initial dosages needed by their patients.
In this study, researchers at Vanderbilt University Medical Center (Nashville, Tenn.) explored the relative impact of polymorphisms in the genes that encode cytochrome P-450 2C9 (CYP2CP) and vitamin K epoxide reductase (VKORC1), two enzymes involved in warfarin metabolism. "Our study showed that during the first weeks of warfarin therapy, variation in the VKORC1 gene is a more important contributor to sensitivity to warfarin than variation in the CYP2C9 gene," said the study’s senior author, C. Michael Stein, M.D., associate chief of clinical pharmacology at Vanderbilt.
Variants of both CYP2CP and VKORC1 were associated with warfarin dose requirements after an initial two weeks of therapy but not with the incidence of bleeding episodes. Further studies are needed to determine how CYP2CP and VKORC1 variants may interact with other genetic variations and additional factors that can affect patients’ response to warfarin.
"Warfarin is probably the first example of a widely used drug where we’re predicting variability in a large chunk of the population, and the variability may make a difference in outcome," said Dan Roden, M.D., vice chancellor for personalized medicine, who contributed to the study. "The ultimate goal is to have these kinds of data available at the time of prescription. Imagine a day when we can get your whole genome sequenced fast and cheap. It might even become part of neonatal testing."
|
April 2008 - Table of Contents
Archives