Association of apolipoprotein E genotype with duration of time to achieve a stable warfarin dose in African-American patients.

ABSTRACT

STUDY 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. DESIGN: Retrospective cohort study. SETTING: Pharmacist-managed antithrombosis clinic. PATIENTS Ninety-two African-American adults whose warfarin therapy was initiated between September 2, 1999, and July 8, 2009. MEASUREMENTS AND MAIN 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)Hquinone 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. CONCLUSION: 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.