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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 epsilon4/epsilon4 and genotype epsilon3/epsilon4 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 epsilon3/epsilon3. Patients homozygous for the epsilon2 allele required 3.5 mg (95%CI: 0.1 to 6.9) acenocoumarol per week more than patients with genotype epsilon3/epsilon3. The acenocoumarol maintenance dose showed a gene dose effect of the epsilon4 allele, but not of the epsilon2 allele. No significant dose difference was observed for phenprocoumon, possibly because of low numbers. CONCLUSION: The ApoE genotype affects the dose requirements of acenocoumarol.

Original publication




Journal article


Pharmacogenet Genomics

Publication Date





69 - 74


Acenocoumarol, Aged, Alleles, Anticoagulants, Apolipoproteins E, Blood Coagulation, Cohort Studies, Coumarins, Female, Genotype, Homozygote, Humans, International Normalized Ratio, Male, Middle Aged, Phenprocoumon, Time Factors, Vitamin K