576
Views
0
CrossRef citations to date
0
Altmetric
Review

The Pharmacogenetics of Coumarin Therapy

, , &
Pages 503-513 | Published online: 24 Nov 2005

Bibliography

  • Hirsh J , DalenJ, AndersonDR et al.: Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest119, 8S–21S (2001).
  • Linder MW : Genetic mechanisms for hypersensitivity and resistance to the anticoagulant warfarin.Clin. Chim. Acta308, 9–15 (2001).
  • Tabrizi AR , ZehnbauerBA, BoreckiIB, McGrathSD, BuchmanTG, FreemanBD: The frequency and effects of cytochrome P450 (CYP) 2C9 polymorphisms in patients receiving warfarin.J. Am. Coll. Surg.194, 267–273 (2002).
  • Gage BF , EbyC, MilliganPE, BanetGA, DuncanJR, McLeodHL: Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin.Thromb. Haemost.91, 87–94 (2004).
  • Beyth R , MilliganPE, GageBF: Risk factors for bleeding in patients taking coumarins:Curr. Hem. Reports. 1, 41–49 (2002).
  • Crowther MA , GinsbergJB, KearonC et al.: A randomized trial comparing 5 mg and 10 mg warfarin loading doses: Arch. Intern. Med.159, 46–48 (1999).
  • Kovacs MJ , RodgerM, AndersonDR et al.: Comparison of 10 mg and 5 mg warfarin initiation nomograms together with low-molecular-weight heparin for out-patient treatment of acute venous thromboembolism: a randomized, double-blind, controlled trial. Ann. Intern. Med.138, 714–719 (2003).
  • Fennerty A , DolbenJ, ThomasP et al.: Flexible induction dose regimen for warfarin and prediction of maintenance dose. Br. Med. J. (Clin. Res. Ed.)288, 1268–1270 (1984).
  • Voora D , EbyC, LinderMW et al.: Prospective dosing of warfarin based on cytochrome P450 2C9 genotype. Thromb. Haemost.93, 700–705 (2005).
  • Park BK : Warfarin: metabolism and mode of action.Biochem. Pharmacol.37, 19–27 (1988).
  • Li T , ChangCY, JinDY, LinPJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature427, 541–544 (2004).
  • Rost S , FreginA, IvaskeviciusV et al.: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency Type 2. Nature427, 537–541 (2004).
  • Miners JO , BirkettDJ: Cytochrome P4502C9: an enzyme of major importance in human drug metabolism.Br. J. Clin. Pharmacol.45, 525–538 (1998).
  • Redman AR : Implications of cytochrome P450 2C9 polymorphism on warfarin metabolism and dosing.Pharmacotherapy21, 235–242 (2001).
  • Takahashi H , EchizenH: Pharmacogenetics of warfarin elimination and its clinical implications.Clin. Pharmacokinet.40, 587–603 (2001).
  • Thijssen HH , Flinois J-P, Beaune PH: Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions in human liver microsomes. Drug Metab. Dispos.28, 1284–1290 (2000).
  • Thijssen HH , BaarsLG, Drittij-Reijnders MJ: Stereoselective aspects in the pharmacokinetics and pharmacodynamics of acenocoumarol and its amino and acetamido derivatives in the rat. Drug Metab. Dispos.13, 593–597 (1985).
  • Takahashi H , WilkinsonGR, PadriniR, EchizenH: CYP2C9 and oral anticoagulation therapy with acenocoumarol and warfarin: similarities yet differences.Clin. Pharmacol. Ther.75, 376–380 (2004).
  • Meinertz T , KasperW, KahlC, JahnchenE: Anticoagulant activity of the enantiomers of acenocoumarol.Br. J. Clin. Pharmacol.5, 187–188 (1978).
  • Ufer M , SvenssonJO, KrauszKW, Gelboin HV, Rane A, Tybring G: Identification of cytochromes P450 2C9 and 3A4 as the major catalysts of phenprocoumon hydroxylation in vitro. Eur. J. Clin. Pharmacol.60, 173–182 (2004).
  • Kirchheiner J , UferM, WalterEC et al.: Effects of CYP2C9 polymorphisms on the pharmacokinetics of R- and S-phenprocoumon in healthy volunteers. Pharmacogenetics14, 19–26 (2004).
  • Fihn SD , GadisseurAA, PasterkampE et al.: Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus phenprocoumon. Thromb. Haemost.90, 260–266 (2003).
  • Williams PA , CosmeJ, WardA, Angove HC, Matak Vinkovic D, Jhoti H: Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature424, 464–468 (2003).
  • Gotoh O : Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences.J. Biol. Chem.267, 83–90 (1992).
  • Lee S , KimJM, ChungCS, ChoKJ, Kim JH: Polymorphism in CYP2C9 as a non-critical factor of warfarin dosage adjustment in Korean patients. Arch. Pharm. Res.26, 967–972 (2003).
  • Takahashi H , WilkinsonGR, CaracoY et al.: Population differences in S-warfarin metabolism between CYP2C9 genotype-matched Caucasian and Japanese patients. Clin. Pharmacol. Ther.73, 253–263 (2003).
  • Shintani M , IeiriI, InoueK et al: Genetic polymorphisms and functional characterization of the 5′-flanking region of the human CYP2C9 gene: in vitro and in vivo studies. Clin. Pharmacol. Ther.70, 175–182 (2001).
  • Takahashi H , IeiriI, WilkinsonGR et al.: 5′-flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients. Blood103, 3055–3057 (2004).
  • Rettie AE , TaiG, VeenstraDL et al.: CYP2C9 exon 4 mutations and warfarin dose phenotype in Asians. Blood101, 2896–2897 (2003).
  • Furuya H , Fernandez-SalgueroP, Gregory W et al: Genetic polymorphism of CYP2C9 and its effect on warfarin maintenance dose requirement in patients undergoing anticoagulation therapy. Pharmacogenetics5, 389–392 (1995).
  • Yamazaki H , InoueK, ChibaK et al.: Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys- and Leu-variants in the oxidation of warfarin, flurbiprofen, and diclofenac by human liver microsomes. Biochem. Pharmacol.56, 243–251 (1998).
  • Rettie AE , HainingRL, BajpaiM, LevyRH: A common genetic basis for idiosyncratic toxicity of warfarin and phenytoin.Epilepsy Res.35, 253–255 (1999).
  • Sullivan-Klose TH , GhanayemBI, BellDA et al: The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics6, 341–349 (1996).
  • Yamazaki H , InoueK, ShimadaT: Roles of two allelic variants (Arg144Cys and Ile359Leu) of cytochrome P4502C9 in the oxidation of tolbutamide and warfarin by human liver microsomes.Xenobiotica28, 103–115 (1998).
  • Crespi CL , MillerVP: The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase.Pharmacogenetics7, 203–210 (1997).
  • Henne KR , GaedigkA, GuptaG, LeederJS, RettieAE: Chiral phase analysis of warfarin enantiomers in patient plasma in relation to CYP2C9 genotype.J. Chromatogr. B Biomed. Sci. Appl.710, 143–148 (1998).
  • Kaminsky LS , de Morais SM, Faletto MB, Dunbar DA, Goldstein JA: Correlation of human cytochrome P4502C substrate specificities with primary structure: warfarin as a probe. Mol. Pharmacol.43, 234–239 (1993).
  • Dickmann LJ , RettieAE, Kneller MB et al.: Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African–Americans. Mol. Pharmacol.60, 382–387 (2001).
  • Lee CR , GoldsteinJA, PieperJA: Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in vitro and human data.Pharmacogenetics12, 251–263 (2002).
  • Takahashi H , KashimaT, NomotoS et al.: Comparisons between in vitro and in vivo metabolism of (S)-warfarin: catalytic activities of cDNA-expressed CYP2C9, its Leu359 variant and their mixture versus unbound clearance in patients with the corresponding CYP2C9 genotypes. Pharmacogenetics8, 365–373 (1998).
  • Takanashi K , TainakaH, KobayashiK, YasumoriT, HosakawaM, ChibaK: CYP2C9 Ile359 and Leu359 variants: enzyme kinetic study with seven substrates.Pharmacogenetics10, 95–104 (2000).
  • Steward DJ , HainingRL, HenneKR et al.: Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics7, 361–367 (1997).
  • Thijssen HH , RitzenB: Acenocoumarol pharmacokinetics in relation to cytochrome P450 2C9 genotype.Clin. Pharmacol. Ther.74, 61–68 (2003).
  • Imai J , IeiriI, MamiyaK et al.: Polymorphism of the cytochrome P450 (CYP)2C9 gene in Japanese epileptic patients: genetic analysis of the CYP2C9 locus. Pharmacogenetics10, 85–89 (2000).
  • Ieiri I , TainakaH, MoritaT et al.: Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis. Ther. Drug Monit.22, 237–244 (2000).
  • Aithal GP , DayCP, KestevenPJ, DalyAK: Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications.Lancet353, 717–719 (1999).
  • Higashi MK , VeenstraDL, KondoLM et al.: Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA287, 1690–1698 (2002).
  • Hermida J , ZarzaJ, AlbercaI et al.: Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P450 CYP2C9 on sensitivity to acenocoumarol. Blood99, 4237–4239 (2002).
  • Joffe HV , XuR, JohnsonFB, LongtineJ, KucherN, GoldhaberSZ: Warfarin dosing and cytochrome P450 2C9 polymorphisms.Thromb. Haemost.91, 1123–1128 (2004).
  • Siguret V , GouinI, GolmardJL, GeoffroyS, AndreuxJP, PautasE: Cytochrome P450 2C9 polymorphisms (CYP2C9) and warfarin maintenance dose in elderly patients.Rev. Med. Interne25, 271–274 (2004).
  • Margaglione M , ColaizzoD, D’AndreaG et al.: Genetic modulation of oral anticoagulation with warfarin. Thromb. Haemost.84, 775–778 (2000).
  • Spreafico M , PeyvandiF, PizzottiD, Moia M, Mannucci PM: Warfarin and acenocoumarol dose requirements according to CYP2C9 genotyping in North Italian patients. J. Thromb. Haemost.1, 2252–2253 (2003).
  • Scordo MG , PengoV, SpinaE, DahlML, GusellaM, PadriniR: Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance.Clin. Pharmacol. Ther.72, 702–710 (2002).
  • Taube J , HalsallD, BaglinT: Influence of cytochrome P450 CYP2C9 polymorphisms on warfarin sensitivity and risk of overanticoagulation in patients on long-term treatment.Blood96, 1816–1819 (2000).
  • Tassies D , FreireC, PijoanJ et al.: Pharmacogenetics of acenocoumarol: cytochrome P450 CYP2C9 polymorphisms influence dose requirements and stability of anticoagulation. Haematologica87, 1185–1191 (2002).
  • Schalekamp T , van Geest-Daalderop JH, de Vries-Goldschmeding H, Conemans J, Bernsen Mj M, de Boer A: Acenocoumarol stabilization is delayed in CYP2C93 carriers. Clin. Pharmacol. Ther.75, 394–402 (2004).
  • Visser LE , van Vliet M, van Schaik RH et al.: The risk of overanticoagulation in patients with cytochrome P450 CYP2C9*2 or CYP2C9*3 alleles on acenocoumarol or phenprocoumon. Pharmacogenetics14, 27–33 (2004).
  • Thijssen HH , VerkooijenIW, FrankHL: The possession of the CYP2C9*3 allele is associated with low dose requirement of acenocoumarol.Pharmacogenetics10, 757–760 (2000).
  • Hummers-Pradier E , HessS, AdhamIM, PapkeT, PieskeB, KochenMM: Determination of bleeding risk using genetic markers in patients taking phenprocoumon.Eur. J. Clin. Pharmacol.59, 213–219 (2003).
  • Palareti G , LealiN, CoccheriS et al.: Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian study on complications of oral anticoagulant therapy. Lancet348, 423–428 (1996).
  • Fihn SD , CallahanCM, MartinDC, McDonell MB, Henikoff JG, White RH: The risk for and severity of bleeding complications in elderly patients treated with warfarin. The National Consortium of Anticoagulation Clinics. Ann. Intern. Med.124, 970–979 (1996).
  • Hylek EM , SingerDE: Risk factors for intracranial hemorrhage in out-patients taking warfarin.Ann. Intern. Med.120, 897–902 (1994).
  • Oden A , FahlenM: Oral anticoagulation and risk of death: a medical record linkage study.BMJ325, 1073–1075 (2002).
  • Azar AJ , CannegieterSC, DeckersJW et al.: Optimal intensity of oral anticoagulant therapy after myocardial infarction. J. Am. Coll. Cardiol.27, 1349–1355 (1996).
  • Cannegieter SC , RosendaalFR, Wintzen AR, van der Meer FJM, Vandenbroucke JP, Briet E: Optimal oral anticoagulant therapy in patients with mechanical heart valves. N. Engl. J. Med.333, 11–7 (1995).
  • Hylek EM , GoAS, ChangY et al.: Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N. Engl. J. Med.349, 1019–1026 (2003).
  • Waterman AD , MilliganPE, BayerL, Banet GA, Gatchel SK, Gage BF: Effect of warfarin nonadherence on control of the international normalized ratio. Am. J. Health Syst. Pharm.61, 1258–1264 (2004).
  • Schalekamp T , OosterhofM, van Meegen E et al.: Effects of cytochrome P450 2C9 polymorphisms on phenprocoumon anticoagulation status. Clin. Pharmacol. Ther.76, 409–417 (2004).
  • Gurwitz JH , AvornJ, Ross-DegnanD, ChoodnovskiyI, AnsellJ: Aging and the anticoagulant response to warfarin therapy.Ann. Intern. Med.116, 901–904 (1992).
  • Loebstein R , YonathH, PelegD et al.: Interindividual variability in sensitivity to warfarin – nature or nurture? Clin. Pharmacol. Ther. 70, 159–164 (2001).
  • Shepherd AM , HewickDS, MorelandTA, StevensonIH: Age as a determinant of sensitivity to warfarin.Br. J. Clin. Pharmacol.4, 315–320 (1977).
  • Mungall DR , LuddenTM, MarshallJ, HawkinsDW, TalbertRL, CrawfordMH: Population pharmacokinetics of racemic warfarin in adult patients.J. Pharmacokinet. Biopharm.13, 213–227 (1985).
  • Wynne H , CopeL, KellyP, WhittinghamT, EdwardsC, KamaliF: The influence of age, liver size and enantiomer concentrations on warfarin requirements.Br. J. Clin. Pharmacol.40, 203–207 (1995).
  • Kamali F , KhanTI, KingBP et al.: Contribution of age, body size, and CYP2C9 genotype to anticoagulant response to warfarin. Clin. Pharmacol. Ther.75, 204–212 (2004).
  • Blann A , HewittJ, SiddiquiF, BarefordD: Racial background is a determinant of average warfarin dose required to maintain the INR between 2.0 and 3.0.Br. J. Haematol.107, 207–209 (1999).
  • James AH , BrittRP, RaskinoCL, ThompsonSG: Factors affecting the maintenance dose of warfarin.J. Clin. Pathol.45, 704–706 (1992).
  • Absher RK , MooreME, ParkerMH: Patient-specific factors predictive of warfarin dosage requirements.Ann. Pharmacother.36, 1512–1517 (2002).
  • Rieder MJ , ReinerAP, GageBF et al.: VKORC1 haplotypes predict warfarin dose. N. Engl. J. Med.352, 15–23 (2005).
  • Alving BM , StricklerMP, KnightRD, Barr CF, Berenberg JL, Peck CC: Hereditary warfarin resistance. Investigation of a rare phenomenon. Arch. Intern. Med.145, 499–501 (1985).
  • Kamali F , EdwardsC, ButlerTJ, Wynne HA: The contribution of plasma (R)- & (S)-warfarin and vitamin K concentrations to intra-individual variability in anticoagulation. Thromb. Haemost.83, 349–350 (2000).
  • Harrington DJ , UnderwoodS, MorseC, ShearerMJ, TuddenhamEG, Mumford AD: Pharmacodynamic resistance to warfarin associated with a Val66Met substitution in vitamin K epoxide reductase complex subunit 1. Thromb. Haemost.93, 23–26 (2005).
  • D’Andrea G , D’AmbrosioRL, Di Perna P et al.: A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood105, 645–649 (2005).
  • Bodin L , VerstuyftC, TregouetDA et al.: Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity.Blood106, 135–140 (2005).
  • Wajih N , SaneDC, HutsonSM, WallinR: The inhibitory effect of calumenin on the vitamin K-dependent γ-carboxylation system. Characterization of the system in normal and warfarin-resistant rats.J. Biol. Chem.279, 25276–25283 (2004).
  • Wallin R , HutsonSM, CainD, SweattA, SaneDC: A molecular mechanism for genetic warfarin resistance in the rat.Faseb. J.15, 2542–2544 (2001).
  • Shikata E , IeiriI, IshiguroS et al.: Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and γ-glutamyl carboxylase) gene variants with warfarin sensitivity. Blood103, 2630–2635 (2004).
  • D’Ambrosio RL , D’AndreaG, CappucciF et al: Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin. Haematologica89, 1510–1516 (2004).
  • Chu K , WuSM, StanleyT, StaffordDW, HighKA: A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism.J. Clin. Invest.98, 1619–1625 (1996).
  • D’Andrea G , D’AmbrosioR L, Di Perna P et al.: A polymorphism in VKORC1 gene is associated with an inter-individual variability in the dose-anticoagulant effect of warfarin. Blood 105(2), 645–649 (2004).
  • Francis CW , BerkowitzSD, CompPC et al.: Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N. Engl. J. Med.349, 1703–1712 (2003).
  • Francis CW , DavidsonBL, BerkowitzSD et al: Ximelagatran versus warfarin for the prevention of venous thromboembolism after total knee arthroplasty. A randomized, double-blind trial. Ann. Intern. Med.137, 648–655 (2002).
  • Inoue K , YamazakiH, ImiyaK, AkasakaS, GuengerichFP, ShimadaT: Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4’-hydroxylation activities in livers of Japanese and Caucasian populations.Pharmacogenetics7, 103–113 (1997).
  • Scordo MG , AklilluE, YasarU, DahlML, SpinaE, Ingelman-SundbergM: Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a black African population.Br. J. Clin. Pharmacol.52, 447–450 (2001).
  • Yasar U , EliassonE, DahlML, JohanssonI, Ingelman-SundbergM, SjoqvistF: Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a Swedish population.Biochem. Biophys. Res. Commun.254, 628–631 (1999).
  • Aynacioglu AS , BrockmollerJ, BauerS et al.: Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br. J. Clin. Pharmacol.48, 409–415 (1999).
  • Garcia-Martin E , MartinezC, LaderoJM, GamitoFJ, AgundezJA: High frequency of mutations related to impaired CYP2C9 metabolism in a Caucasian population.Eur. J. Clin. Pharmacol.57, 47–49 (2001).
  • Peyvandi F , SpreaficoM, SiboniSM, Moia M, Mannucci PM: CYP2C9 genotypes and dose requirements during the induction phase of oral anticoagulant therapy. Clin. Pharmacol. Ther.75, 198–203 (2004).
  • Nasu K , KubotaT, IshizakiT: Genetic analysis of CYP2C9 polymorphism in a Japanese population.Pharmacogenetics7, 405–409 (1997).
  • Takahashi H , KashimaT, NomizoY et al.: Metabolism of warfarin enantiomers in Japanese patients with heart disease having different CYP2C9 and CYP2C19 genotypes. Clin. Pharmacol. Ther.63, 519–528 (1998).
  • Wang SL , HuangJ, LaiMD, TsaiJJ: Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese.Pharmacogenetics5, 37–42 (1995).
  • Yoon YR , ShonJH, KimMK et al.: Frequency of cytochrome P450 2C9 mutant alleles in a Korean population. Br. J. Clin. Pharmacol.51, 277–280 (2001).
  • Sconce EA , KhanTI, WynneHA et al.: The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood (2005) (Epub ahead of print).

Website

  • http://www.immm.ki.se/CYP alleles The Human CYP Allele Nomenclature Committee website.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.