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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4106-4112.
Prepublished online as a Blood First Edition Paper on February 4, 2008; DOI 10.1182/blood-2007-11-122010.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
CYP4F2 genetic variant alters required warfarin dose
Michael D. Caldwell1,
Tarif Awad2,
Julie A. Johnson3,
Brian F. Gage4,
Mat Falkowski2,
Paul Gardina2,
Jason Hubbard2,
Yaron Turpaz2,
Taimour Y. Langaee3,
Charles Eby4,
Cristi R. King4,
Amy Brower5,
John R. Schmelzer6,
Ingrid Glurich7,
Humberto J. Vidaillet8,
Steven H. Yale9,
Kai Qi Zhang10,
Richard L. Berg11, and
James K. Burmester10
1 Department of Surgery, Marshfield Clinic, Marshfield, WI;
2 Affymetrix, Santa Clara, CA;
3 University of Florida, Gainesville;
4 Washington University, St Louis, MO;
5 Third Wave Technologies, Madison, WI;
6 Health Services Research Center, Marshfield Clinic Research Foundation, Marshfield, WI;
7 Office of Scientific Writing and Publications, Marshfield Clinic Research Foundation, Marshfield, WI;
Departments of8 Cardiology, and
9 General Internal Medicine, Marshfield Clinic, Marshfield, WI;
10 Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI; and
11 Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI
Warfarin is an effective, commonly prescribed anticoagulant used to treat and prevent thrombotic events. Because of historically high rates of drug-associated adverse events, warfarin remains underprescribed. Further, interindividual variability in therapeutic dose mandates frequent monitoring until target anticoagulation is achieved. Genetic polymorphisms involved in warfarin metabolism and sensitivity have been implicated in variability of dose. Here, we describe a novel variant that influences warfarin requirements. To identify additional genetic variants that contribute to warfarin requirements, screening of DNA variants in additional genes that code for drug-metabolizing enzymes and drug transport proteins was undertaken using the Affymetrix drug-metabolizing enzymes and transporters panel. A DNA variant (rs2108622; V433M) in cytochrome P450 4F2 (CYP4F2) was associated with warfarin dose in 3 independent white cohorts of patients stabilized on warfarin representing diverse geographic regions in the United States and accounted for a difference in warfarin dose of approximately 1 mg/day between CC and TT subjects. Genetic variation of CYP4F2 was associated with a clinically relevant effect on warfarin requirement.
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