[Cytochrome P4502C9(CYP2C9) gene polymorphism and safety of therapy with warfarin]

Kardiologiia. 2008;48(3):52-7.
[Article in Russian]

Abstract

Aim of the study was to investigate frequency and influence of alleles CYP2C9*2 and CYP2C9*3 on pharmacokinetics, pharmacodynamics and dosing regimen of warfarin and on development of hemorrhagic complications. We included 84 patients (mean age 62,8 +/- 10,5 years). Duration of follow-up varied between 1 month and 1 year. Carriage of allele variants was determined by polymerase chain reaction, measurement of plasma wafarin concentration was carried out with the help of high performance liquid chromatography. Wild type (CYP2C9*1/*1) was found in 68% of patients; overall frequency of 2C9*1/*1, *l/*3, *2/*2, *3/*3, *2/*3 genotypes was 32%. Average maintenance doses of warfarin for patients with allele variants CYP 2C9 *2 and 2C9 *3 were 3.6 and 3.1 mg/day, respectively, what was significantly lower than in wild type homozygotes (6.1 mg/day). Wild type homozygotes (1) had the highest warfarin clearance (3,51 ml/min). In carriers of 2C9 *2(2) and 2C9 *3(3) warfarin clearance was significantly lower (2.42 and 1.82 ml/min; p1 - 2 = 0,05; p1 - 3 = 0,0008). In carriers of allele variants CYP2C9*2, CYP2C9*3 values of international normalized ratio > 3,0 were met more often, especially in carriers of CYP2C9*3 (in 100% of cases) vs. 28% in wild type homozygotes (p=0,02). Carriers of CYP2C9*3 compared with wild type homozygotes had more hemorrhagic complications (67% and 16%, respectively, p=0,0008). Thus cytochrome P450 2C9 gene polymorphism influences frequency of development of hemorrhagic complications, metabolic clearance, and magnitude of warfarin maintenance dose.

Publication types

  • Comparative Study
  • English Abstract

MeSH terms

  • Anticoagulants / pharmacokinetics
  • Anticoagulants / therapeutic use*
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Blood Coagulation / drug effects
  • Blood Coagulation / genetics*
  • Cytochrome P-450 CYP2C9
  • DNA / genetics*
  • Female
  • Follow-Up Studies
  • Hemorrhage / blood
  • Hemorrhage / chemically induced
  • Hemorrhage / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Risk Factors
  • Thrombosis / blood
  • Thrombosis / drug therapy
  • Thrombosis / genetics*
  • Time Factors
  • Treatment Outcome
  • Warfarin / administration & dosage
  • Warfarin / pharmacokinetics
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Warfarin
  • DNA
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases