title: Patients with an ApoE epsilon4 allele require lower doses of coumarin anticoagulants.
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 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.
  
  
  CONCLUSIONS
  The ApoE genotype affects the dose requirements of acenocoumarol.
authors.affiliation: Pharmacoepidemiology Unit, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
authors.forename: Paul H
authors.initials: PH
authors.lastname: Trienekens
authors.forename: Peter A G M
authors.initials: PA
authors.lastname: De Smet
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Vulto
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Bruno H Ch
authors.initials: BH
authors.lastname: Stricker
mesh_terms: D000074:Acenocoumarol / Q000494:pharmacology; D000368:Aged; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage*; D001057:Apolipoproteins E / Q000235:genetics*; D001777:Blood Coagulation; D015331:Cohort Studies; D003374:Coumarins / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000494:pharmacology; D013997:Time Factors; D014812:Vitamin K / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D001057:Apolipoproteins E; D003374:Coumarins; D014812:Vitamin K; C030123:coumarin; D000074:Acenocoumarol; D010644:Phenprocoumon