AIMS: The influence of CYP2C9 and VKORC1 on warfarin dose, time to target International Normalized Ratio (INR), time to stabilization, and risk of over-anticoagulation (INR: > 4) was assessed after adjustment for clinical factors, intraindividual variation in environmental factors and unobserved heterogeneity. MATERIALS & METHODS: Common CYP2C9 and VKORC1 polymorphisms were assessed in 302 European-Americans and 273 African-Americans receiving warfarin. Race-stratified multivariable analyses evaluated the influence of CYP2C9 and VKORC1 on warfarin response. RESULTS & CONCLUSION: CYP2C9 and VKORC1 accounted for up to 30% of the variability in warfarin dose among European-Americans and 10% among African-Americans. Neither CYP2C9 nor VKORC1 influenced the time to target INR or stabilization among patients of either race, and neither influenced the risk of over-anticoagulation among African-Americans. The risk of over-anticoagulation was higher among European-Americans with variant VKORC1 1173C/T (p < 0.01) and marginally significant among those with variant CYP2C9 (p = 0.08) genotype. Although CYP2C9 and VKORC1 genotyping can facilitate individualized initiation of warfarin dose in African and European-Americans, the ability to predict the risk of over-anticoagulation is inconsistent across race. Identification of other factors that can predict such risk consistently in a racially diverse group will facilitate individualized maintenance of warfarin therapy.
AIMS: The influence of CYP2C9 and VKORC1 on warfarin dose, time to target International Normalized Ratio (INR), time to stabilization, and risk of over-anticoagulation (INR: > 4) was assessed after adjustment for clinical factors, intraindividual variation in environmental factors and unobserved heterogeneity. MATERIALS & METHODS: Common CYP2C9 and VKORC1 polymorphisms were assessed in 302 European-Americans and 273 African-Americans receiving warfarin. Race-stratified multivariable analyses evaluated the influence of CYP2C9 and VKORC1 on warfarin response. RESULTS & CONCLUSION:CYP2C9 and VKORC1 accounted for up to 30% of the variability in warfarin dose among European-Americans and 10% among African-Americans. Neither CYP2C9 nor VKORC1 influenced the time to target INR or stabilization among patients of either race, and neither influenced the risk of over-anticoagulation among African-Americans. The risk of over-anticoagulation was higher among European-Americans with variant VKORC11173C/T (p < 0.01) and marginally significant among those with variant CYP2C9 (p = 0.08) genotype. Although CYP2C9 and VKORC1 genotyping can facilitate individualized initiation of warfarin dose in African and European-Americans, the ability to predict the risk of over-anticoagulation is inconsistent across race. Identification of other factors that can predict such risk consistently in a racially diverse group will facilitate individualized maintenance of warfarin therapy.
Authors: John F Carlquist; Benjamin D Horne; Joseph B Muhlestein; Donald L Lappé; Bryant M Whiting; Matthew J Kolek; Jessica L Clarke; Brent C James; Jeffrey L Anderson Journal: J Thromb Thrombolysis Date: 2006-12 Impact factor: 2.300
Authors: David L Veenstra; Joyce H S You; Mark J Rieder; Federico M Farin; Hui-Wen Wilkerson; David K Blough; Gregory Cheng; Allan E Rettie Journal: Pharmacogenet Genomics Date: 2005-10 Impact factor: 2.089
Authors: Elaine M Hylek; James D'Antonio; Carmella Evans-Molina; Carol Shea; Lori E Henault; Susan Regan Journal: Stroke Date: 2006-03-09 Impact factor: 7.914
Authors: M A Perera; E Gamazon; L H Cavallari; S R Patel; S Poindexter; R A Kittles; D Nicolae; N J Cox Journal: Clin Pharmacol Ther Date: 2011-01-26 Impact factor: 6.875
Authors: Y Liu; H Jeong; H Takahashi; K Drozda; S R Patel; N L Shapiro; E A Nutescu; L H Cavallari Journal: Clin Pharmacol Ther Date: 2012-02-29 Impact factor: 6.875
Authors: Walter Ageno; Alexander S Gallus; Ann Wittkowsky; Mark Crowther; Elaine M Hylek; Gualtiero Palareti Journal: Chest Date: 2012-02 Impact factor: 9.410
Authors: Nita A Limdi; T Mark Beasley; Michael R Crowley; Joyce A Goldstein; Mark J Rieder; David A Flockhart; Donna K Arnett; Ronald T Acton; Nianjun Liu Journal: Pharmacogenomics Date: 2008-10 Impact factor: 2.533