title: Cytochrome P450 2C9 polymorphism and acenocoumarol therapy.
abstract: BACKGROUND
  Oral anticoagulants, in Hungary acenocoumarol being the one exclusively used, have a low therapeutic index and a high bleeding complication rate. The cytochrome P450 2C9 enzyme plays an important role in their metabolism.
  
  
  OBJECTIVE
  To investigate the influence of CYP2C9 polymorphism on the occurrence of bleeding complications related to acenocoumarol therapy.
  
  
  METHODS
  Genotyping of 421 patients (183 men and 238 women, mean age 66.2+/-11.8 years), who had been taking acenocoumarol for at least 6 months, was performed. Based on patient history and laboratory data, the correlations between genotype and acenocoumarol dose and bleeding complications were retrospectively analysed.
  
  
  RESULTS
  In 145 patients bearing alleles with reduced activity (CYP2C9*2 and/or *3), the optimal dose of acenocoumarol was significantly (p<0.001) lower than in patients with the wild type allele (2.12+/-0.96 mg/day and 2.90+/-1.46 mg/day, respectively). In comparison with wild type allele patients, the mean daily acenocoumarol dose was lower in the CYP2C9*2 group, and the lowest in *3 bearers. Although the occurrence of minor bleeding complications in patients with the variant allele was significantly (p <0.005) higher (OR=1.99 [CI: 1.20-3.33]) than in other patients, there was no difference in major bleeding complications.
  
  
  CONCLUSIONS
  Patients bearing CYP2C9 alleles with reduced enzymatic activity have a lower acenocoumarol requirement. In patients with CYP2C9*2 and *3 alleles the frequency of minor bleeding complications and the occurrence of high INR values were significantly higher, but there was no difference in the rate of major bleedings.
authors.affiliation: 2nd Department of Internal Medicine--Cardiology, Pandy Kalman Bekes County Hospital, Semmelweis u. 1., P.O. Box 46., H-5700 Gyula, Hungary. mark@pandy.hu
authors.forename: Laszlo
authors.initials: L
authors.lastname: Mark
authors.forename: Janos
authors.initials: J
authors.lastname: Marki-Zay
authors.forename: Lajos
authors.initials: L
authors.lastname: Fodor
authors.forename: Ildiko
authors.initials: I
authors.lastname: Hajdara
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Paragh
authors.forename: Andras
authors.initials: A
authors.lastname: Katona
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects*; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic
chemical_list: D000925:Anticoagulants; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000074:Acenocoumarol