title: Association of apolipoprotein E genotype with duration of time to achieve a stable warfarin dose in African-American patients.
abstract: OBJECTIVE
  To test the hypothesis that genotypes for proteins affecting vitamin K availability influence the duration of time required to achieve a stable warfarin dose in African-American patients.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Pharmacist-managed antithrombosis clinic.
  
  
  METHODS
  Ninety-two African-American adults whose warfarin therapy was initiated between September 2, 1999, and July 8, 2009.
  
  
  RESULTS
  During a routine anticoagulation clinic visit, a sample was collected from each patient for genetic analysis. genotyping was performed for the following variants: apolipoprotein E ε2, ε3, and ε4; NAD(P)H:quinone oxidoreductase (NQO1)*2; cytochrome P450 (CYP) 4F2 V433M; CYP2C9*2, *3, *5, *8, and *11; and vitamin K epoxide reductase complex 1 (VKORC1) -1639G>A. Patients' medical records were then reviewed, and data were collected retrospectively for each anticoagulation clinic visit during the first 6 months of warfarin therapy or until dose stabilization. The median time required to reach a stable warfarin dose, defined as the dose that produced therapeutic anticoagulation for three consecutive clinic visits, was 83 days. Compared with the 46 patients who achieved a stable warfarin dose within 83 days, the 46 patients who required longer durations for dose stabilization had a higher frequency of the apolipoprotein E ε3/ε3 genotype (37% vs 59%, p=0.037). Sixty-one percent of patients with the ε3/ε3 genotype versus 40% of those with an ε2 or ε4 allele had a delay in achieving a stable dose (p=0.037). Neither the CYP4F2 nor NQO1 genotype was associated with warfarin dose stabilization.
  
  
  CONCLUSIONS
  Our data support the hypothesis that the apolipoprotein E genotype is associated with duration of time to reach a stable warfarin dose in African-American patients. Further insight into the genetic effects on warfarin dose stabilization could reveal novel methods to improve anticoagulation control during the warfarin initiation period.
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, 60612-7230, USA. humma@uic.edu
authors.forename: Larisa H
authors.initials: LH
authors.lastname: Cavallari
authors.forename: Christopher
authors.initials: C
authors.lastname: Butler
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.forename: Nargis
authors.initials: N
authors.lastname: Wardak
authors.forename: Shitalben R
authors.initials: SR
authors.lastname: Patel
authors.forename: Marlos A G
authors.initials: MA
authors.lastname: Viana
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Shapiro
authors.forename: Edith A
authors.initials: EA
authors.lastname: Nutescu
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000494:pharmacology; D001057:Apolipoproteins E / Q000235:genetics*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010595:Pharmacists / Q000458:organization & administration; D010597:Pharmacogenetics; D012189:Retrospective Studies; D013997:Time Factors; D014859:Warfarin / Q000008:administration & dosage* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D001057:Apolipoproteins E; D014859:Warfarin