( e can have quite a large effect on bloo...)Genetic variation alters response to common anti-clotting drug

Doctors primarily use information about a patient's sex, age, weight, and medical history to set the initial warfarin dose. However, it can take several months of clinic visits and needle pricks to determine an individual's ideal dose. Scientists know that variations in a gene encoding the CYP2C9 enzyme that metabolizes warfarin account for about 10 percent of the difference in people's responses to the drug, but tests for these genetic variations are not routinely performed.

Rettie and his colleague Mark J. Rieder, Ph.D., an assistant professor in the University of Washington's department of genome sciences and first author of the paper, wanted to better understand the genetic basis for variability in warfarin response. "If you want to predict dose, you need to know more about the genes that control variability," explained Rieder.

The team focused on another gene: vitamin K epoxide reductase (VKORC1), which makes a protein that helps control clotting and is the key target of warfarin. The researchers analyzed the VKORC1 gene's DNA sequence in 186 patients on a stabilized dose of warfarin. They searched for common DNA variations responsible for changing the gene's activity and the amount of protein it made.

"We did find genetic variations that appear to turn up the gene or turn it down," said Rieder.

By matching the genetic variations to actual warfarin doses, the scientists discovered that people with a particular variation of the VKORC1 gene generally took similar doses of warfarin.

The genetic variations divided patients into three main groups: low, high, and intermediate dose. The intermediate group included people with a combination of the low- and high-dose gene versions. These results, the researchers said, suggest that informa
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Source:NIH/National Institute of General Medical Sciences