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Invited Commentary
August 2014

Warfarin, Genes, and the (Health Care) Environment

Author Affiliations
  • 1Department of Medicine, University of California, San Francisco
  • 2Department of Epidemiology and Biostatistics, University of California, San Francisco
  • 3Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California
  • 4Department of Medicine, Stanford University School of Medicine, Stanford, California
JAMA Intern Med. 2014;174(8):1338-1339. doi:10.1001/jamainternmed.2014.1227

Despite the introduction of several novel oral anticoagulants, warfarin remains the most widely used anticoagulation agent worldwide. Physicians have extensive experience with warfarin, it is inexpensive, its effects are easily reversible, and its activity can be monitored with a simple blood test. However, warfarin has a narrow therapeutic index and requires active management.

Day-to-day variability in an individual’s response to warfarin is partially determined by diet, comorbidities, and interactions with other medications. Genetic variation also affects warfarin dosing; carriers of reduced-function polymorphisms of CYP2C9 have decreased clearance of warfarin and therefore require lower maintenance doses, and carriers of polymorphisms in VKORC1 have altered sensitivity to vitamin K antagonists.1

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