Use of pharmacogenetics to guide warfarin therapy.
The Human Genome Project heralds new opportunities for pharmacogenetics, the use of genetics to individualize the application of pharmaceuticals in the practice of medicine (1-3). Single nucleotide polymorphisms (SNPs) and other genetic variants in genes responsible for absorption, metabolism and excretion have been associated with alterations in drug disposition or effect. Warfarin is a potential target for pharmacogenetics-based dosing because of its wide use, variability in individual response, high prevalence of genetic variants and severity of adverse drug reactions (4). The genotype assays for genetic variants relevant to warfarin are widely used and are being developed for commercial use (5), making the promise of a pharmacogenetics-based approach a near reality.
Voora
Deepak
D
Departments of Medicine and Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
McLeod
Howard L
HL
Eby
Charles
C
Gage
Brian F
BF
D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D006801:Humans; D066298:In Vitro Techniques; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases