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Genetic variation alters response to common anti-clotting drug

Millions of people take the anticoagulant drug warfarin to prevent harmful clotting after a heart attack, stroke, or major surgery. But the proper dose of warfarin can vary greatly and can be hard to predict. Some of this variability may boil down to a recently identified gene involved in blood clotting, according to a new study published in the June 2 issue of The New England Journal of Medicine.

By looking at the genetic makeup of people on warfarin, researchers at the University of Washington in Seattle and Washington University in St. Louis learned that variations in a gene involved in blood clotting may explain why certain people require a lower or higher dose of warfarin to get its full benefits. This line of work ultimately could help doctors determine each patient's warfarin dose more quickly and precisely.

The study, part of the NIH Pharmacogenetics Research Network, was supported by three components of the National Institutes of Health (NIH): the National Institute of General Medical Sciences (NIGMS); the National Heart, Lung, and Blood Institute (NHLBI); and the National Institute of Environmental Health Sciences (NIEHS).

"This research points to the value of pharmacogenetics, the study of how genetic variations can alter people's responses to medicines," said NIH Director Elias A. Zerhouni, M.D. "It shows one important way in which we are beginning to apply knowledge about the human genome for treating disease and improving human health."

Warfarin (trade names include CoumadinTM) is the most commonly prescribed oral anti-clotting drug. Allan E. Rettie, Ph.D., University of Washington professor of medicinal chemistry and senior author of the paper, estimated that 2 million people in the United States take warfarin on any given day.

Despite its wide use, physicians find the drug challenging to prescribe.

"There is a narrow window between too much and too little effect," explained Rettie. "A small change in dos
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Source:NIH/National Institute of General Medical Sciences


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