Pharmacogenetics of acenocoumarol: CYP2C9 *2 and VKORCI c.-l 639G>A, 497C>G, 1173C>T, and 3730G>A variants influence drug dose in anticoagulated patients

Thrombosis and Haemostasis

Volumn 101, Issue 3, 2009, Pages 591-593

  Verde, Zoraida ^a   Santiago, Catalina ^a   Valle, Beatriz ^b   Ana, Fernández Santander ^a   Bandrés, Fernando ^b   Calvo, Elpidio ^b   Ruiz, Jonatan R ^c   Lucia, Alejandro ^a   Gallego, Félix Gómez ^a  

^a UNIVERSIDAD EUROPEA DE MADRID   (Spain)

^b Breast Pathology Center   (Spain)

^c HOSPITAL CLÍNICO SAN CARLOS   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ACENOCOUMAROL; CYTOCHROME P450 2C9; GENOMIC DNA; MENADIONE EPOXIDE REDUCTASE; OXIDOREDUCTASE; UNCLASSIFIED DRUG; ANTICOAGULANT AGENT; CYP2C9 PROTEIN, HUMAN; MENADIONE EPOXIDASE; MIXED FUNCTION OXIDASE; UNSPECIFIC MONOOXYGENASE;

ADULT; AGED; ANTICOAGULANT THERAPY; ARTICLE; BLEEDING; CEREBROVASCULAR ACCIDENT; CYP2C9 GENE; DEEP VEIN THROMBOSIS; DRUG MEGADOSE; DRUG METABOLISM; ENZYME POLYMORPHISM; FEMALE; GENE; GENE FREQUENCY; HEART ATRIUM FIBRILLATION; HUMAN; HUMAN TISSUE; INTERNATIONAL NORMALIZED RATIO; LOW DRUG DOSE; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MALE; PHARMACOGENETICS; PRIORITY JOURNAL; THROMBOEMBOLISM; VKORC1 GENE; GENETIC POLYMORPHISM; GENETICS; LETTER; MIDDLE AGED; RISK FACTOR;

ACENOCOUMAROL; ANTICOAGULANTS; ARYL HYDROCARBON HYDROXYLASES; FEMALE; HUMANS; MALE; MIDDLE AGED; MIXED FUNCTION OXYGENASES; POLYMORPHISM, GENETIC; RISK FACTORS;

EID: 62549089149     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH08-09-0578     Document Type: Article

References (20)

1. Hirsh J, Dalen JE, Anderson DR. et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1998; 114: 4455-4695.
2. Gage BF, Eby CS. Pharmacogenetics and anticoagulant therapy. J Thromb Thrombolysis 2003; 16: 73-78.
3. Oldenburg J, Bevans CG, Freging A, et al. Current pharmacogenetic developments in oral anticoagulation therapy: The influence of variant VKORC1 and CYP2CP alleles. Thromb Haemost 2007; 98: 570-578.
4. Thijssen HH, Flinois JP. Beaune PH. Cytochrome P4502C9 is the principal catalystic of racemic acenocoumarol hydroxylation reactions in human liver microsomes. Drug Metab Dispos 2000; 28: 1284-1290.
5. Hermida J, Zarza J. Alberca I, et al. Differential effects of 2C9*3 and 2CP*2 variants of cytochrome P-450CYP2C9 on sensitivity to acenocoumarol. Blood 2002; 99: 4237-4239.
6. Tassies D, Freire C, Pijoan J, et al. Pharmacogenetics of acenocoumarol: cytochrome P450 CYP2C9 polymorphisms influence dose requirements and stability of anticoagulation, Haematologica 2002; 87: 1185-1191.
7. Rieder MJ, Reiner AP, Gage BF, et al. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose, N Engl J Med 2005; 352: 2285-2293.
8. D'Andrea G, D'Ambrosio RL, Di Perna R et al, A polymorphism in the VKORC 1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 2005; 105: 645 -649.
9. Geisen C, Watzka M, Sittinger K, et al, VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation. Thromb Haemost 2005; 94: 773-779.
10. Yuan HY. Chen JJ, Lee MT, et al. A novel functional VKORC 1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet 2005: 14: 1745-1751.
11. Montes M, Ruiz de Gaona E, Martinez-González MA. et al. The c.-1639G>A polymorphism of the VKCORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients, Br J Haematol 2006; 133: 183-187.
12. Bodin L, Verstuyft C, Tregouet DA, et al. Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood 2005; 106: 135-140.
13. Reitsma PH. van der Heijden JF, Groot AP, et al. A C1173T dimorphism in the VKCOR1 gene determined coumarin sensitivity and bleeding risk. PloS Med 2005; 2:e312.
14. Schwarz UI, Ritchie MD, Bradford Y, et al. Genetic determinants of response to warfarin during initial anticoagulation. N Engl J Med 2008; 358: 999-1008.
15. Meckley LM, Wittkowsky AK, Rieder MJ, et al. An analysis of the relative effects of VKORC1 and CYP2C9 variants on anticoagulation related outcomes in warfarin-treated patients. Thromb Haemost 2008; 100: 229-239.
16. Sanderson S, Emery J, Higgins J. CYP2C9 gene variants, drug dose, and bleeding risk in warfarintreated patients: a HuGEnet systematic review and meta-analysis. Genet Med 2005; 7: 97-104,
17. Taube J, Halsall D. Baglin T. Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-coagulation in patients on longterm treatment. Blood 2000; 96: 1816-1819.
18. Yin T. Miyata T, Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 -Rationale and perspectives. Thromb Res 2007; 120: 1-10.
19. Sehalekamp T. Brasse BP. Roijers JF, et al. VKORC 1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin Pharmacol Ther 2006; 80: 13-22.
20. Spreaf ico M, Lodigiani C, van LY, Pizzotti D, et al. Effects of CYP2C9 and VKORC 1 on INR variations and dose requirements during initial phase of anticoagulant therapy, Pharmacogenomics 2008; 9: 1237-1250.