Patients with an ApoE ϵ4 allele require lower doses of coumarin anticoagulants

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Abstract
Objective Vitamin K is an essential cofactor for the synthesis of several blood coagulation factors. It has been suggested that the apolipoprotein E (ApoE) genotype has profound effects on vitamin K status. Therefore, we investigated whether this common genetic polymorphism influenced dose requirements and effects of coumarin anticoagulants. Methods We did a cohort study in 1637 patients from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon. Results To attain the same level of anticoagulation, patients with genotype ε4/ε4 and genotype ε3/ε4 required respectively 3.4 mg (95%CI: −6.0 to −0.9) and 0.8 mg (95%CI: −1.6 to 0.1) acenocoumarol per week less than patients with genotype ε3/ε3. Patients homozygous for the ε2 allele required 3.5 mg (95%CI: 0.1 to 6.9) acenocoumarol per week more than patients with genotype ε3/ε3. The acenocoumarol maintenance dose showed a gene dose effect of the ε4 allele, but not of the ε2 allele. No significant dose difference was observed for phenprocoumon, possibly because of low numbers. Conclusion The ApoE genotype affects the dose requirements of acenocoumarol.