Genetics determine optimal drug dose of common ant...( (WASHINGTON August 21 2007) Genetic...)

(WASHINGTON, August 21, 2007) Genetic testing can be used to help personalize the therapeutic dosage of warfarin, a commonly-used anticoagulant, according to research published in the September 1, 2007, issue of Blood, the journal of the American Society of Hematology. This result represents one of the first applications of using an individuals genetic information to guide personal medical care.

Because individuals metabolize drugs differently, varying doses of warfarin are needed for the drug to be effective in each patient. Too much warfarin can cause severe bleeding, and too little can cause dangerous blood clots. Currently, there is little guidance for predicting how much of the drug a person will need. Physicians have had to roughly estimate an initial dose of warfarin and then continually monitor a patients International Normalized Ratio (INR) value (a measure of how fast the blood clots), during treatment to tweak the dosage by trial and error.

For the first time, a group of St. Louis researchers combined the standard INR method with genetic testing to predict the therapeutic warfarin dose. Since warfarin is often prescribed after major orthopedic surgery to prevent blood clots in the legs, the study followed 92 adults undergoing either total hip or knee replacement at the Washington University Medical Center, who had never previously taken the anticoagulant.

Prior to warfarin treatment, the researchers collected blood samples and each patients medical history. The blood tests were used to examine variations in two genes, CYP2C9 and VKORC1, that may affect warfarin dosing. Variants in CYP2C9 impair the bodys breakdown of warfarin; variants in VKORC1 cause increased warfarin sensitivity. The patients were assigned initial doses of warfarin based on clinical factors and their genotype. The researchers followed the patients until successful treatment outcomes were achieved several weeks later.

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