title: Warfarin response and vitamin K epoxide reductase complex 1 in African Americans and Caucasians.
abstract: The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 (VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and -1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans (-12.10 mg/week+/-4.93; P=0.02) and Caucasians (-14.41 mg/week+/-3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio >3 (odds ratio=3.10; 95% confidence interval: 1.73-5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over-anticoagulation among African Americans.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics & Epidemiology, University of Pennsylvania School of Medicine, and Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
authors.forename: H
authors.initials: H
authors.lastname: Schelleman
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: C
authors.initials: C
authors.lastname: Kealey
authors.forename: A S
authors.initials: AS
authors.lastname: Whitehead
authors.forename: J
authors.initials: J
authors.lastname: Christie
authors.forename: M
authors.initials: M
authors.lastname: Price
authors.forename: C M
authors.initials: CM
authors.lastname: Brensinger
authors.forename: C W
authors.initials: CW
authors.lastname: Newcomb
authors.forename: C F
authors.initials: CF
authors.lastname: Thorn
authors.forename: F F
authors.initials: FF
authors.lastname: Samaha
authors.forename: S E
authors.initials: SE
authors.lastname: Kimmel
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D016001:Confidence Intervals; D065729:Cytochrome P-450 CYP2C9; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage / Q000494:pharmacology*; D044465:White People / Q000235:genetics
chemical_list: D000925:Anticoagulants; D001057:Apolipoproteins E; D014859:Warfarin; D004247:DNA; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases