title: Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin.
abstract: The association of CYP2C9 and VKORC1 1173C/T genotype and risk of hemorrhage among African Americans and European Americans is presented. This association was evaluated using Cox proportional hazard regression with adjustment for demographics, comorbidity, and time-varying covariates. Forty-four major and 203 minor hemorrhages occurred over 555 person-years among 446 patients (60.6+/-15.6 years, 50% men, 227 African Americans). The variant CYP2C9 genotype conferred an increased risk for major (hazard ratio (HR) 3.0; 95% confidence interval (CI): 1.1-8.0) but not minor (HR 1.3; 95% CI: 0.8-2.1) hemorrhage. The risk of major hemorrhage was 5.3-fold (95% CI: 0.4-64.0) higher before stabilization of therapy, 2.2-fold (95% CI: 0.7-6.5) after stabilization, and 2.4-fold (95% CI: 0.8-7.4) during all periods when anticoagulation was not stable. The variant VKORC1 1173C/T genotype did not confer a significant increase in risk for major (HR 1.7; 95% CI: 0.7-4.4) or minor (HR 0.8; 95% CI: 0.5-1.3) hemorrhage. The variant CYP2C9 genotype is associated with an increased risk of major hemorrhage, which persists even after stabilization of therapy.
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA. nlimdi@uab.edu
authors.forename: N A
authors.initials: NA
authors.lastname: Limdi
authors.forename: G
authors.initials: G
authors.lastname: McGwin
authors.forename: J A
authors.initials: JA
authors.lastname: Goldstein
authors.forename: T M
authors.initials: TM
authors.lastname: Beasley
authors.forename: D K
authors.initials: DK
authors.lastname: Arnett
authors.forename: B K
authors.initials: BK
authors.lastname: Adler
authors.forename: M F
authors.initials: MF
authors.lastname: Baird
authors.forename: R T
authors.initials: RT
authors.lastname: Acton
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044383:Black People / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006470:Hemorrhage / Q000139:chemically induced* / Q000208:ethnology; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000009:adverse effects* / Q000378:metabolism; D044465:White People / Q000235:genetics*; D001741:Black or African American
chemical_list: D000925:Anticoagulants; D014859:Warfarin; 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