Influence of CYP2C9 and VKORC1 on warfarin response during initiation of therapy

Blood Cells, Molecules, and Diseases

Volumn 43, Issue 1, 2009, Pages 119-128

  Limdi, N A ^a   Wiener, H ^b   Goldstein, J A ^b   Acton, R T ^c   Beasley, T M ^b  

^a The University of Alabama at Birmingham   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c University of Alabama at Birmingham   (United States)

Author keywords

African American; CYP2C9; European American; Hemorrhage; Over anticoagulation; Percent time in target range; Pharmacogenetics; VKORC1

Indexed keywords

CYTOCHROME P450 2C9; MENADIONE EPOXIDE REDUCTASE; OXIDOREDUCTASE; UNCLASSIFIED DRUG; WARFARIN;

ADULT; AFRICAN AMERICAN; ANTICOAGULANT THERAPY; ARTERY THROMBOSIS; ARTICLE; CONTROLLED STUDY; DEEP VEIN THROMBOSIS; DEMOGRAPHY; DOSE CALCULATION; DRUG RESPONSE; ETHNIC DIFFERENCE; EUROPEAN AMERICAN; FEMALE; GENETIC VARIABILITY; GENOTYPE; HUMAN; INTERNATIONAL NORMALIZED RATIO; LIFESTYLE; LUNG EMBOLISM; MAJOR CLINICAL STUDY; MALE; PHARMACOGENETICS; PREDICTION; PRIORITY JOURNAL; THROMBOEMBOLISM; TREATMENT DURATION; VENOUS THROMBOEMBOLISM;

AFRICAN AMERICANS; AGED; ANTICOAGULANTS; ARYL HYDROCARBON HYDROXYLASES; COHORT STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENOTYPE; HEMORRHAGE; HUMANS; INTERNATIONAL NORMALIZED RATIO; MALE; MIDDLE AGED; MIXED FUNCTION OXYGENASES; PHARMACOGENETICS; POLYMORPHISM, GENETIC; PROSPECTIVE STUDIES; RISK FACTORS; WARFARIN;

EID: 67650267115     PISSN: 10799796     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcmd.2009.01.019     Document Type: Article

References (53)

1. Ansell JE O.L., and Wittkowsky A.K. Managing Oral Anticoagulation Therapy: Clinical and Operational Guidelines Lippincott Williams & Wilkins (2005), St. Louis, MO
2. Ansell J., Hollowell J., Pengo V., Martinez-Brotons F., Caro J., and Drouet L. Descriptive analysis of the process and quality of oral anticoagulation management in real-life practice in patients with chronic non-valvular atrial fibrillation: the international study of anticoagulation management (ISAM). J. Thromb. Thrombolysis 23 (2007) 83-91
3. Chiquette E., Amato M.G., and Bussey H.I. Comparison of an anticoagulation clinic with usual medical care: anticoagulation control, patient outcomes, and health care costs. Arch. Intern. Med. 158 (1998) 1641-1647
4. Wittkowsky A.K. Effective anticoagulation therapy: defining the gap between clinical studies and clinical practice. Am. J. Manag. Care 10 (2004) S297-S306 discussion S312-S317
5. Wittkowsky A.K., and Devine E.B. Frequency and causes of overanticoagulation and underanticoagulation in patients treated with warfarin. Pharmacotherapy 24 (2004) 1311-1316
6. Hylek E.M., Go A.S., Chang Y., Jensvold N.G., Henault L.E., Selby J.V., and Singer D.E. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N. Engl. J. Med. 349 (2003) 1019-1026
7. Hylek E.M., and Singer D.E. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann. Intern. Med. 120 (1994) 897-902
8. Hylek E.M., Skates S.J., Sheehan M.A., and Singer D.E. An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N. Engl. J. Med. 335 (1996) 540-546
9. Aquilante C.L., Langaee T.Y., Lopez L.M., Yarandi H.N., Tromberg J.S., Mohuczy D., Gaston K.L., Waddell C.D., Chirico M.J., and Johnson J.A. Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements. Clin. Pharmacol. Ther. 79 (2006) 291-302
10. Bodin L., Verstuyft C., Tregouet D.A., Robert A., Dubert L., Funck-Brentano C., Jaillon P., Beaune P., Laurent-Puig P., Becquemont L., and Loriot M.A. Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood 106 (2005) 135-140
11. Borgiani P., Ciccacci C., Forte V., Romano S., Federici G., and Novelli G. Allelic variants in the CYP2C9 and VKORC1 loci and interindividual variability in the anticoagulant dose effect of warfarin in Italians. Pharmacogenomics 8 (2007) 1545-1550
12. D'Andrea G., D'Ambrosio R.L., Di Perna P., Chetta M., Santacroce R., Brancaccio V., Grandone E., and Margaglione M. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 105 (2005) 645-649
13. Gage B.F., Eby C., Johnson J.A., Deych E., Rieder M.J., Ridker P.M., Milligan P.E., Grice G., Lenzini P., Rettie A.E., Aquilante C.L., Grosso L., Marsh S., Langaee T., Farnett L.E., Voora D., Veenstra D.L., Glynn R.J., Barrett A., and McLeod H.L. Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clin. Pharmacol. Ther. 84 (2008) 326-331
14. Geisen C., Watzka M., Sittinger K., Steffens M., Daugela L., Seifried E., Muller C.R., Wienker T.F., and Oldenburg J. VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation. Thromb. Haemost. 94 (2005) 773-779
15. Herman D., Peternel P., Stegnar M., Breskvar K., and Dolzan V. The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. Thromb. Haemost. 95 (2006) 782-787
16. Montes R., Ruiz de Gaona E., Martinez-Gonzalez M.A., Alberca I., and Hermida J. The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br. J. Haematol. 133 (2006) 183-187
17. Mushiroda T., Ohnishi Y., Saito S., Takahashi A., Kikuchi Y., Saito S., Shimomura H., Wanibuchi Y., Suzuki T., Kamatani N., and Nakamura Y. Association of VKORC1 and CYP2C9 polymorphisms with warfarin dose requirements in Japanese patients. J. Hum. Genet. 51 (2006) 249-253
18. Obayashi K., Nakamura K., Kawana J., Ogata H., Hanada K., Kurabayashi M., Hasegawa A., Yamamoto K., and Horiuchi R. VKORC1 gene variations are the major contributors of variation in warfarin dose in Japanese patients. Clin. Pharmacol. Ther. 80 (2006) 169-178
19. Rieder M.J., Reiner A.P., Gage B.F., Nickerson D.A., Eby C.S., McLeod H.L., Blough D.K., Thummel K.E., Veenstra D.L., and Rettie A.E. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. New Engl. J. Med. 352 (2005) 2285-2293
20. Takahashi H., Wilkinson G.R., Nutescu E.A., Morita T., Ritchie M.D., Scordo M.G., Pengo V., Barban M., Padrini R., Ieiri I., Otsubo K., Kashima T., Kimura S., Kijima S., and Echizen H. Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans. Pharmacogenet Genomics 16 (2006) 101-110
21. Wadelius M., Chen L.Y., Downes K., Ghori J., Hunt S., Eriksson N., Wallerman O., Melhus H., Wadelius C., Bentley D., and Deloukas P. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J. 5 (2005) 262-270
22. Yuan H.Y., Chen J.J., Lee M.T., Wung J.C., Chen Y.F., Charng M.J., Lu M.J., Hung C.R., Wei C.Y., Chen C.H., Wu J.Y., and Chen Y.T. A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum. Mol. Genet. 14 (2005) 1745-1751
23. Loebstein R., Vecsler M., Kurnik D., Austerweil N., Gak E., Halkin H., and Almog S. Common genetic variants of microsomal epoxide hydrolase affect warfarin dose requirements beyond the effect of cytochrome P450 2C9. Clin. Pharmacol. Ther. 77 (2005) 365-372
24. Sconce E.A., Khan T.I., Wynne H.A., Avery P., Monkhouse L., King B.P., Wood P., Kesteven P., Daly A.K., and Kamali F. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 106 (2005) 2329-2333
25. Veenstra D.L., You J.H., Rieder M.J., Farin F.M., Wilkerson H.W., Blough D.K., Cheng G., and Rettie A.E. Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population. Pharmacogenetics Genomics 15 (2005) 687-691
26. Kealey C., Chen Z., Christie J., Thorn C.F., Whitehead A.S., Price M., Samaha F.F., and Kimmel S.E. Warfarin and cytochrome P450 2C9 genotype: possible ethnic variation in warfarin sensitivity. Pharmacogenomics 8 (2007) 217-225
27. Schelleman H., Chen Z., Kealey C., Whitehead A.S., Christie J., Price M., Brensinger C.M., Newcomb C.W., Thorn C.F., Samaha F.F., and Kimmel S.E. Warfarin response and vitamin K epoxide reductase complex 1 in African Americans and Caucasians. Clin. Pharmacol. Ther. 81 (2007) 742-747
28. Limdi N.A., Goldstein J.A., Blaisdell J.A., Beasley T.M., Rivers C.A., and Acton R.T. Influence of CYP2C9 Genotype on warfarin dose among African American and European Americans. Personalized Medicine 4 (2007) 157-169
29. Millican E.A., Lenzini P.A., Milligan P.E., Grosso L., Eby C., Deych E., Grice G., Clohisy J.C., Barrack R.L., Burnett R.S., Voora D., Gatchel S., Tiemeier A., and Gage B.F. Genetic-based dosing in orthopedic patients beginning warfarin therapy. Blood 110 (2007) 1511-1515
30. Voora D., Eby C., Linder M.W., Milligan P.E., Bukaveckas B.L., McLeod H.L., Maloney W., Clohisy J., Burnett R.S., Grosso L., Gatchel S.K., and Gage B.F. Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype. Thromb. Haemost. 93 (2005) 700-705
31. Anderson J.L., Horne B.D., Stevens S.M., Grove A.S., Barton S., Nicholas Z.P., Kahn S.F., May H.T., Samuelson K.M., Muhlestein J.B., and Carlquist J.F. Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation 116 (2007) 2563-2570
32. Caraco Y., Blotnick S., and Muszkat M. CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. Clin. Pharmacol. Ther. 83 (2008) 460-470
33. Schwarz U.I., Ritchie M.D., Bradford Y., Li C., Dudek S.M., Frye-Anderson A., Kim R.B., Roden D.M., and Stein C.M. Genetic determinants of response to warfarin during initial anticoagulation. N. Engl. J. Med. 358 (2008) 999-1008
34. Limdi N., McGwin G., Goldstein J., Beasley T., Arnett D., Adler B., Baird M., and Acton R. Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Mol. Ther. 83 (2008) 312-321
35. Guo S.W., and Thompson E.A. Performing the exact test of Hardy-Weinberg proportion for multiple alleles. Biometrics 48 (1992) 361-372
36. Limdi N.A., Arnett D.K., Goldstein J.A., Beasley T.M., McGwin G., Adler B.K., and A. R.T. Influence of CYP2C9 and VKORC1 polymorphisms on warfarin dose, anticoagulation attainment and maintenance among European American and African Americans. Pharmacogenomics 9 (2008) 511-526
37. Fihn S.D., McDonell M., Martin D., Henikoff J., Vermes D., Kent D., and White R.H. Risk factors for complications of chronic anticoagulation. A multicenter study. Warfarin Optimized Outpatient Follow-up Study Group. Ann. Intern. Med. 118 (1993) 511-520
38. C.F. Ake, and A.L. Carpenter, Extending the Use of PROC PHREG in Survival Analysis Proceedings of the 11th Annual Western Users of SAS SAS Institute Inc, Cary, NC:, 2003.
39. Therneau T.M., and Grambsch P.M. Multiple events per subject. In: Therneau T.M., and Grambsch P.M. (Eds). Modeling Survival Data: Extending the Cox Model (Statistics for Biology and Health) (2001), Springer-Verlag, New York, New York 169-229
40. Limdi N.A., Beasley T.M., Allison D.B., Rivers C.A., and Acton R.T. Racial differences in the prevalence of Factor V Leiden mutation among patients on chronic warfarin therapy. Blood Cells Mol. Dis. 37 (2006) 100-106
41. Hillman M.A., Wilke R.A., Yale S.H., Vidaillet H.J., Caldwell M.D., Glurich I., Berg R.L., Schmelzer J., and Burmester J.K. A prospective, randomized pilot trial of model-based warfarin dose initiation using CYP2C9 genotype and clinical data. Clin. Med. Res. 3 (2005) 137-145
42. Schalekamp T., Brasse B.P., Roijers J.F., van Meegen E., van der Meer F.J., van Wijk E.M., Egberts A.C., and de Boer A. VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement. Clin. Pharmacol. Ther. 81 (2007) 185-193
43. Schalekamp T., Brasse B.P., Roijers J.F., Chahid Y., van Geest-Daalderop J.H., de Vries-Goldschmeding H., van Wijk E.M., Egberts A.C., and de Boer A. VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin. Pharmacol. Ther. 80 (2006) 13-22
44. Wadelius M., and Pirmohamed M. Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J. (2006)
45. S.J. Booth, SL, J.L. Weihrauch, G. Ferland, Vitamin K (phylloquinone) content of foods. J Food Consump Anla 6 (1993) 109-120.
46. Couris R., Tataronis G., McCloskey W., Oertel L., Dallal G., Dwyer J., and Blumberg J.B. Dietary vitamin K variability affects international normalized ratio (INR) coagulation indices. Int J Vitam Nutr Res 76 (2006) 65-74
47. Schurgers L.J., Shearer M.J., Hamulyak K., Stocklin E., and Vermeer C. Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects. Blood 104 (2004) 2682-2689
48. Kimmel S.E., Christie J., Kealey C., Chen Z., Price M., Thorn C.F., Brensinger C.M., Newcomb C.W., and Whitehead A.S. Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans. Pharmacogenomics J. 8 (2008) 53-60
49. Sconce E.A., Daly A.K., Khan T.I., Wynne H.A., and Kamali F. APOE genotype makes a small contribution to warfarin dose requirements. Pharmacogenet Genomics 16 (2006) 609-611
50. Kimura R., Kokubo Y., Miyashita K., Otsubo R., Nagatsuka K., Otsuki T., Sakata T., Nagura J., Okayama A., Minematsu K., Naritomi H., Honda S., Sato K., Tomoike H., and Miyata T. Polymorphisms in vitamin K-dependent gamma-carboxylation-related genes influence interindividual variability in plasma protein C and protein S activities in the general population. Int J Hematol 84 (2006) 387-397
51. Rieder M.J., Reiner A.P., and Rettie A.E. Gamma-glutamyl carboxylase (GGCX) tagSNPs have limited utility for predicting warfarin maintenance dose. J Thromb Haemost 5 (2007) 2227-2234
52. Kimura R., Miyashita K., Kokubo Y., Akaiwa Y., Otsubo R., Nagatsuka K., Otsuki T., Okayama A., Minematsu K., Naritomi H., Honda S., Tomoike H., and Miyata T. Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients. Thromb. Res. 120 (2007) 181-186
53. Vecsler M., Loebstein R., Almog S., Kurnik D., Goldman B., Halkin H., and Gak E. Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin. Thromb. Haemost. 95 (2006) 205-211