Use of pharmacogenetics to guide warfarin therapy

Drugs of Today

Volumn 40, Issue 3, 2004, Pages 247-257

  Voora, Deepak ^a   McLeod, Howard L ^a   Eby, Charles ^a   Gage, Brian F ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BLOOD CLOTTING FACTOR 10; BLOOD CLOTTING FACTOR 7; BLOOD CLOTTING FACTOR 9; CYTOCHROME P450 2C9; PROTHROMBIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); WARFARIN;

ANTICOAGULANT THERAPY; ASIAN; BLEEDING; CAUCASIAN; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME POLYMORPHISM; ETHNIC DIFFERENCE; HUMAN; MAINTENANCE DRUG DOSE; NEGRO; PHARMACOGENETICS; REVIEW; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM;

ANTICOAGULANTS; ARYL HYDROCARBON HYDROXYLASES; HUMANS; PHARMACOGENETICS; POLYMORPHISM, GENETIC; WARFARIN;

EID: 2342464850     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2004.40.3.820088     Document Type: Review

References (84)

1. Collins, F.S., McKusick, V.A. Implications of the human genome project for medical science. JAMA 2001, 285: 540-4.
2. Collins, F.S. Shattuck lecture-medical and societal consequences of the human genome project. N Engl J Med 1999, 341: 28-37.
3. Evans, W.E., Mcleod, H. L. Pharmacogenomics-drug disposition, drug targets, and side effects. N Engl J Med 2003, 348: 538-49.
4. Phillips, K.A., Veenstra, D.L., Oren, E., Lee, J.K., Sadee, W. Potential role of pharmacogenomics in reducing adverse drug reactions: A systematic review. JAMA 2001, 286: 2270-9.
5. Evans, W.E., Relling, M.V. Pharmacogenomics: Translating functional genomics into rational therapeutics. Science 1999, 286: 487-91.
6. Hirsh, J., Dalen, J., Anderson, D.R. et al. Oral anticoagulants: Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001, 119: 8S-21S.
7. Linder, M.W. Genetic mechanisms for hypersensitivity and resistance to the anticoagulant warfarin. Clin Chim Acta 2001, 308: 9-15.
8. Tabrizi, A.R., Zehnbauer, B.A., Borecki, I.B., McGrath, S.D., Buchman, T.G., Freeman, B.D. The frequency and effects of cytochrome p450 (cyp) 2c9 polymorphisms in patients receiving warfarin. J Am Coll Surg 2002, 194: 267-73.
9. Gage, B.F., Eby, C., Milligan, P.E., Banet, G.A., Duncan, J.R., Mcleod, H.L. Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost 2004, 91: 87-94.
10. Crowther, M.A., Ginsberg, J.B., Kearon, C. et al. A randomized trial comparing 5-mg and 10-mg warfarin loading doses. Arch Intern Med 1999, 159: 46-8.
11. Kovacs, M.J., Rodger, M., Anderson, D.R. et al. Comparison of 10-mg and 5-mg warfarin initiation nomograms together with low-molecular-weight heparin for outpatient treatment of acute venous thromboembolism. A randomized, double-blind, controlled trial. Ann Intern Med 2003, 138: 714-9.
12. Fennerty, A., Dolben, J., Thomas, P. et al. Flexible induction dose regimen for warfarin and prediction of maintenance dose. Br Med J (Clin Res Ed) 1984, 288: 1268-70.
13. Park, B.K. Warfarin: Metabolism and mode of action. Biochem Pharmacol 1988, 37: 19-27.
14. Takahashi, H., Echizen, H. Pharmacogenetics of warfarin elimination and its clinical implications. Clin Pharmacokinet 2001, 40: 587-603.
15. Miners, J.O., Birkett, D.J. Cytochrome p4502c9: An enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998, 45: 525-38.
16. Redman, A.R. Implications of cytochrome p450 2c9 polymorphism on warfarin metabolism and dosing. Pharmacotherapy 2001, 21: 235-42.
17. Wilting, J., van Der Giesen, W.F., Janssen, L.H., Weideman, M.M., Otagiri, M., Perrin, J.H. The effect of albumin conformation on the binding of warfarin to human serum albumin. The dependence of the binding of warfarin to human serum albumin on the hydrogen, calcium, and chloride ion concentrations as studied by circular dichroism, fluorescence, and equilibrium dialysis. J Biol Chem 1980, 255: 3032-7.
18. Sanoski, C.A., Bauman, J.L. Clinical observations with the amiodarone/warfarin interaction: Dosing relationships with long-term therapy. Chest 2002, 121: 19-23.
19. 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 1992, 267: 83-90.
20. Human Cytochrome p450 (CYP) Allele Nomenclature Committee home page (http://www.imm.ki.se/cypalleles/), accessed on 3/24/03.
21. Leung, A.Y., Chow, H.C., Kwong, Y.L. et al. Genetic polymorphism in exon 4 of cytochrome p450 cyp2c9 may be associated with warfarin sensitivity in chinese patients. Blood 2001, 98: 2584-7.
22. Rettie, A.E., Tai, G., Veenstra, D.L. et al. Cyp2c9 exon 4 mutations and warfarin dose phenotype in asians. Blood 2003, 101: 2896-7.
23. Rettie, A.E., Wienkers, L.C., González, F.J., Trager, W.F., Korzekwa, K.R. Impaired (s)-warfarin metabolism catalysed by the r144c allelic variant of cyp2c9. Pharmacogenetics 1994, 4: 39-42.
24. Furuya, H., Fernández-Salguero, P., Gregory, W. et al. Genetic polymorphism of cyp2c9 and its effect on warfarin maintenance dose requirement in patients undergoing anticoagulation therapy. Pharmacogenetics 1995, 5: 389-92.
25. Yamazaki, H., Inoue, K., Chiba, K. 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 1998, 56: 243-51.
26. Rettie, A.E., Haining, R.L., Bajpai, M., Levy, R.H. A common genetic basis for idiosyncratic toxicity of warfarin and phenytoin. Epilepsy Res 1999, 35: 253-5.
27. Sullivan-Klose, T.H., Ghanayem, B.I., Bell, D.A. et al. The role of the cyp2c9-leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 1996, 6: 341-9.
28. Yamazaki, H., Inoue, K., Shimada, T. Roles of two allelic variants (arg144cys and ile3591eu) of cytochrome p4502c9 in the oxidation of tolbutamide and warfarin by human liver microsomes. Xenobiotica 1998, 28: 103-15.
29. Crespi, C.L., Miller, V.P. The r144c change in the cyp2c9*2 allele alters interaction of the cytochrome p450 with nadph: Cytochrome p450 oxidoreductase. Pharmacogenetics 1997, 7: 203-10.
30. Henne, K.R., Gaedigk, A., Gupta, G., Leeder, J.S., Rettie, A.E. Chiral phase analysis of warfarin enantiomers in patient plasma in relation to cyp2c9 genotype. J Chromatogr B Biomed Sci Appl 1998, 710: 143-8.
31. Steward, D.J., Haining, R.L., Henne, K.R. et al. Genetic association between sensitivity to warfarin and expression of cyp2c9*3. Pharmacogenetics 1997, 7: 361-7.
32. Kaminsky, L.S., De Morais, S.M., Faletto, M.B., Dunbar, D.A., Goldstein, J.A. Correlation of human cytochrome p4502c substrate specificities with primary structure: Warfarin as a probe. Mol Pharmacol 1993, 43: 234-9.
33. Dickmann, L.J., Rettie, A.E., Kneller, M.B. et al. Identification and functional characterization of a new cyp2c9 variant (cyp2c9*5) expressed among african americans. Mol Pharmacol 2001, 60: 382-7.
34. Takanashi, K., Tainaka, H., Kobayashi, K., Yasumori, T., Hosakawa, M., Chiba, K. Cyp2c9 ile359 and leu359 variants: Enzyme kinetic study with seven substrates. Pharmacogenetics 2000, 10: 95-104.
35. Lee, C.R., Goldstein, J.A., Pieper, J.A. Cytochrome p450 2c9 polymorphisms: A comprehensive review of the in-vitro and human data. Pharmacogenetics 2002, 12: 251-63.
36. Takahashi, H., Kashima, T., Nomoto, S. 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. Pharmacogenetics 1998, 8: 365-73.
37. Takahashi, H., Kashima, T., Nomizo, Y. et al. Metabolism of warfarin enantiomers in japanese patients with heart disease having different cyp2c9 and cyp2c19 genotypes. Clin Pharmacol Ther 1998, 63: 519-28.
38. Imai, J., Ieiri, I., Mamiya, K. et al. Polymorphism of the cytochrome p450 (cyp) 2c9 gene in japanese epileptic patients: Genetic analysis of the cyp2c9 locus. Pharmacogenetics 2000, 10: 85-9.
39. Ieiri, I., Tainaka, H., Morita, T. 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 2000, 22: 237-44.
40. Aithal, G.P., Day, C.P., Kesteven, P.J., Daly, A.K. Association of polymorphisms in the cytochrome p450 cyp2c9 with warfarin dose requirement and risk of bleeding complications. Lancet 1999, 353: 717-9.
41. Higashi, M.K., Veenstra, D.L., Kondo, L.M., et al. Association between cyp2c9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 2002, 287: 1690-8.
42. Hermida, J., Zarza, J., Alberca, I. et al. Differential effects of 2c9*3 and 2c9*2 variants of cytochrome p-450 cyp2c9 on sensitivity to acenocoumarol. Blood 2002, 99: 4237-9.
43. Margaglione, M., Colaizzo, D., D'Andrea, G. et al. Genetic modulation of oral anticoagulation with warfarin. Thromb Haemost 2000, 84: 775-8.
44. Gurwitz, J.H., Avom, J., Ross-Degnan, D., Choodnovskiy, I., Ansell, J. Aging and the anticoagulant response to warfarin therapy. Ann Intern Med 1992, 116: 901-4.
45. Loebstein, R., Yonath, H., Peleg, D. et al. Interindividual variability in sensitivity to warfarin - nature or nurture? Clin Pharmacol Ther 2001, 70: 159-64.
46. Shepherd, A.M., Hewick, D.S., Moreland, T.A., Stevenson, I.H. Age as a determinant of sensitivity to warfarin. Br J Clin Pharmacol 1977, 4: 315-20.
47. Mungall, D.R., Ludden, T.M., Marshall, J., Hawkins, D.W., Talbert, R.L., Crawford, M.H. Population pharmacokinetics of racemic warfarin in adult patients. J Pharmacokinet Biopharm 1985, 13: 213-27.
48. Freeman, B.D., Zehnbauer, B.A., Mcgrath, S., Borecki, I., Buchman, T.G. Cytochrome p450 polymorphisms are associated with reduced warfarin dose. Surgery 2000, 128: 281-5.
49. Blann, A., Hewitt, J., Siddiqui, F., Bareford, D. Racial background is a determinant of average warfarin dose required to maintain the inr between 2.0 and 3.0. Br J Haematol 1999, 107: 207-9.
50. Wynne, H., Cope, L., Kelly, P., Whittingham, T., Edwards, C., Kamali, F. The influence of age, liver size and enantiomer concentrations on warfarin requirements. Br J Clin Pharmacol 1995, 40: 203-7.
51. Absher, R.K., Moore, M.E., Parker, M.H. Patient-specific factors predictive of warfarin dosage requirements. Ann Pharmacother 2002, 36: 1512-7.
52. Raschke, R.A., Reilly, B.M., Guidry, J.R., Fontana, J.R., Srinivas, S. The weight-based heparin dosing nomogram compared with a "standard care" nomogram. A randomized controlled trial. Ann Intern Med 1993, 119: 874-81.
53. Kereveur, A., Leclercq, M., Trossaert, M. et al. Vitamin k metabolism in a patient resistant to vitamin K antagonists. Haemostasis 1997, 27: 168-73.
54. Hulse, M.L. Warfarin resistance: Diagnosis and therapeutic alternatives. Pharmacotherapy 1996, 16: 1009-17.
55. Wallace, M.E., MacSwiney, F.J. A major gene controlling warfarin-resistance in the house mouse. J Hyg (Lond) 1976, 76: 173-81.
56. Greaves, J.H., Ayres, P. Linkages between genes for coat colour and resistance to warfarin in rattus norvegicus. Nature 1969, 224: 284-5.
57. Kohn, M.H., Pelz, H.J., Wayne, R.K. Natural selection mapping of the warfarin-resistance gene. Proc Natl Acad Sci USA 2000, 97: 7911-5.
58. Kohn, M.H., Pelz, H.J. A gene-anchored map position of the rat warfarin-resistance locus, rw, and its orthologs in mice and humans. Blood 2000, 96: 1996-8.
59. Rost, S., Fregin, A., Ivaskevicius, V. et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 2004, 427: 537-41
60. Li, T., Chang, C.Y., Jin, D.Y., Lin, P.J., Khvorova, A., Stafford, D.W. Identification of the gene for vitamin K epoxide reductase. Nature 2004, 427: 541-44.
61. Palareti, G., Leali, N., Coccheri, S. et al. Bleeding complications of oral anticoagulant treatment: An inception-cohort, prospective collaborative study (iscoat). Italian study on complications of oral anticoagulant therapy. Lancet 1996, 348: 423-8.
62. Fihn, S.D., Callahan, C.M., Martin, D.C., McDonell, M.B., Henikoff, J.G., White, R.H. The risk for and severity of bleeding complications in elderly patients treated with warfarin. The national consortium of anticoagulation clinics. Ann Intern Med 1996, 124: 970-9.
63. Beyth, R., Milligan, P.E., Gage, B.F. Risk factors for bleeding in patients taking coumarins. Curr Hem Reports 2002, 1: 41-9.
64. Fihn, S.D., McDonell, M., Martin, D. et al. Risk factors for complications of chronic anticoagulation. A multicenter study. Warfarin optimized outpatient follow-up study group. Ann Intern Med 1993, 118: 511-20.
65. Taube, J., Halsall, D., Baglin, T. Influence of cytochrome p-450 cyp2c9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 2000, 96: 1816-9.
66. Waterman, A.D., Milligan, P.E., Bayer, L., Banet, G.A., Gatchel, S.K., Gage, B.F. Prevalence and predictors of warfarin non-adherence. Am J Health Syst Pharm 2004 (in press).
67. White, R.H., Beyth, R.J., Zhou, H., Romano, P.S. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 1999, 107: 414-24.
68. Hylek, E.M., Singer, D.E. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 1994, 120: 897-902.
69. Goldford, M.B.J., Triscott, M. Solid phase genotyping of the warfarin metabolizing enzyme cyp2c9 with DNA probes. Thromb Haemost 2001, 86: 674.
70. Hiratsuka, M., Agatsuma, Y., Mizugaki, M. Rapid detection of cyp2c9*3 alleles by real-time fluorescence pcr based on sybr green. Mol Genet Metab 1999, 68: 357-62.
71. White, R.H., Hong, R., Venook, A. P. et al. Initiation of warfarin therapy: Comparison of physician dosing with computer-assisted dosing. J Gen Intern Med 1987, 2: 141-8.
72. Romkes, M., Faletto, M.B., Blaisdell, J.A., Raucy, J.L., Goldstein, J.A. Cloning and expression of complementary dnas for multiple members of the human cytochrome p450iic subfamily. Biochemistry 1991, 30: 3247-55.
73. Kidd, R.S., Curry, T.B., Gallagher, S., Edeki, T., Blaisdell, J., Goldstein, J.A. Identification of a null allele of cyp2c9 in an african-american exhibiting toxicity to phenytoin. Pharmacogenetics 2001, 11: 803-8.
74. Goldstein, J. Polymorphisms in the human cyp2c subfamily. Drug Metabolism Reviews 2002, 34: 5.
75. Wang, S.L., Lai, M.D., Lai, M.L., Huang, J.D. R296c and other cyp2d6 mutations in chinese. Pharmacogenetics 1995, 5: 385-8.
76. Inoue, K., Yamazaki, H., Imiya, K., Akasaka, S., Guengerich, F.P., Shimada, T. Relationship between cyp2c9 and 2c19 genotypes and tolbutamide methyl hydroxylation and s-mephenytoin 4′-hydroxylation activities in livers of japanese and caucasian populations. Pharmacogenetics 1997, 7: 103-13.
77. Scordo, M.G., Aklillu, E., Yasar, U., Dahl, M.L., Spina, E., Ingelman-Sundberg, M. Genetic polymorphism of cytochrome p450 2c9 in a caucasian and a black african population. Br J Clin Pharmacol 2001, 52: 447-50.
78. Yasar, U., Eliasson, E., Dahl, M.L., Johansson, I., Ingelman-Sundberg, M., Sjoqvist, F. Validation of methods for cyp2c9 genotyping: Frequencies of mutant alleles in a swedish population. Biochem Biophys Res Commun 1999, 254: 628-31.
79. Aynacioglu, A.S., Brockmoller, J., Bauer, S. et al. Frequency of cytochrome p450 cyp2c9 variants in a turkish population and functional relevance for phenytoin. Br J Clin Pharmacol 1999, 48: 409-15.
80. García-Martín, E., Martínez, C., Ladero, J.M., Gamito, F. J., Agundez, J.A. High frequency of mutations related to impaired cyp2c9 metabolism in a caucasian population. Eur J Clin Pharmacol 2001, 57: 47-9.
81. Nasu, K., Kubota, T., Ishizaki, T. Genetic analysis of cyp2c9 polymorphism in a japanese population. Pharmacogenetics 1997, 7: 405-9.
82. Wang, S.L., Huang, J., Lai, M.D., Tsai, J.J. Detection of cyp2c9 polymorphism based on the polymerase chain reaction in chinese. Pharmacogenetics 1995, 5: 37-42.
83. Yoon, Y.R., Shon, J.H., Kim, M.K. et al. Frequency of cytochrome p450 2c9 mutant alleles in a korean population. Br J Clin Pharmacol 2001, 51: 277-280.
84. Williams, P.A., Cosme, J., Ward, A., Angove, H.C., Matak Vinkovic, D., Jhoti, H. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 2003, 424: 464-8.