Following the exclusive license of the warfarin biomarker, 4F2, by the Marshfield Clinic to Osmetech in November 2007, the Marshfield Clinic Research Foundation, led by Michael D. Caldwell, M.D., Ph.D., has an article published in the peer-reviewed journal, Blood Online, entitled “CYP4F2 genetic variant alters required warfarin dose.”
This demonstrates that the biomarker will help reduce adverse reactions to the commonly-prescribed anticoagulant used to treat and prevent thrombotic events. Because of historically high rates of adverse drug-associated events, warfarin remains under-prescribed due to variability in therapeutic dose among patients which mandates frequent monitoring.
The U.S. Food and Drug Administration (FDA) mandated the re-labeling of warfarin to include genetic testing for known valid markers in two genes (CYP2C9 and VKORC1) involved in warfarin metabolism and sensitivity which impact a patient’s response to warfarin.
The dosing of warfarin is complicated due to its small therapeutic window and is affected by factors including genetics, age, body mass index and gender. If a dose is too high or too low, there is a risk of serious bleeding or clotting events.
The Blood Online article describes a novel variant in a third gene cytochrome P450 4F2 (CYP4F2), discovered by the Marshfield research team, that significantly influences warfarin requirements. The DNA variant in cytochrome CYP4F2 was found to be associated with warfarin dosage in three independent patient groups stabilized on warfarin (n=1054) recruited by the Marshfield Clinic, University of Florida and Washington University.
Adjusting warfarin dosage for this variant could help reduce the serious adverse events caused by incorrect dosage and enable doctors to treat patients in a more effective and individualized manner.