Association of Apolipoprotein E Genotype with Duration of Time to Achieve a Stable Warfarin Dose in African‐American Patients
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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)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.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.
