Extreme warfarin sensitivity in siblings associated with multiple cytochrome P450 polymorphisms.
Warfarin use is complicated by an erratic dose response. Warfarin is metabolized by two distinct subfamilies of the cytochrome P450 (CYP) complex. We describe two siblings with extreme sensitivity to warfarin who share an unusual CYP genotype. These individuals illustrate both the importance of genetics in influencing the metabolism of warfarin as well as the potential utility of genetic testing as a guide to prescribing this medication.
Tabrizi
A R
AR
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
McGrath
S D
SD
Blinder
M A
MA
Buchman
T G
TG
Zehnbauer
B A
BA
Freeman
B D
BD
D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004342:Drug Hypersensitivity / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics; D014859:Warfarin / Q000009:adverse effects* / Q000493:pharmacokinetics
D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D039181:Steroid 16-alpha-Hydroxylase