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Knowledge of genetics improves uncertain medication

Roughly 100,000 Swedes are under treatment with the blood-thinning drug Waran. Patients evince varying sensitivity to Waran, which makes the initiation of treatment a risky balancing act between hemorrhaging and clotting. Now researchers at Uppsala University have developed a model for calculating the appropriate dose before treatment starts. The study appears in the scientific publication New England Journal of Medicine.

Some 20 research teams in four regions of the world have joined together to study whether it is possible to determine the proper dosage of Waran before starting treatment. Data from 5,700 subjects undergoing treatment with Waran were collected from the four parts of the globe. Niclas Eriksson, a statistician at UCR Uppsala Clinical Research Center has developed a model for calculating the right dosage of Waran for individuals of European, African, and Asian origin.

"The findings show that with the aid of two genes, VKORC1 and CYP2C9, it is possible to predict what dosage patients will land at," says Niclas Eriksson.

"Almost half of patients have mutations that entail that they need a slightly lower dose than normal, and a small percentage need a much lower dose," says Mia Wadelius, a physician and researcher in clinical pharmacology, Uppsala University Hospital, who was in charge of collecting the data in Sweden.

The next step will be to test this method on patients in health care. This spring an American clinical test will get underway to study whether custom-tailored treatment increases the certainty in treating patients with Waran. Similar clinical testing will start this autumn in seven countries in Europe. A total of 3,000 patients who are starting treatment with blood-thinning medicines will be recruited. The Swedish part of the study will be directed by Mia Wadelius, and the Waran clinics in Uppsala and Skne will be participating. Patients will start either with a custom-tailored dosage or with the normal dosage and then be compared.

"Even patients receiving a tailored dose need regular tests of the blood's ability to coagulate, since diet and other medicines play a role, but it is our hope that the treatment will be both safer and more secure with tailored dosage," says Mia Wadelius.


Contact: Mia Wadelius
Uppsala University

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