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ObjectiveVitamin 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.MethodsWe did a cohort study in 1637 patients from an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon.ResultsTo 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.ConclusionThe ApoE genotype affects the dose requirements of acenocoumarol.

Original publication




Journal article


Pharmacogenetics and genomics

Publication Date





69 - 74


Pharmacoepidemiology Unit, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.


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