Association of warfarin dose with genes involved in its action and metabolism

Human Genetics

Volumn 121, Issue 1, 2007, Pages 23-34

  Wadelius, Mia ^a   Chen, Leslie Y ^b   Eriksson, Niclas ^c   Bumpstead, Suzannah ^b   Ghori, Jilur ^b   Wadelius, Claes ^d   Bentley, David ^b   McGinnis, Ralph ^b   Deloukas, Panos ^b  

^a UPPSALA UNIVERSITY HOSPITAL   (Sweden)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^c UPPSALA CLINICAL RESEARCH CENTER   (Sweden)

^d UPPSALA UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN E; BLOOD CLOTTING FACTOR 7; BLOOD CLOTTING FACTOR 9; CYTOCHROME P450 2C18; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; EPOXIDE HYDROLASE; FATTY ACID BINDING PROTEIN; GAMMA GLUTAMYL HYDROLASE; MENADIONE EPOXIDE; OROSOMUCOID; PREGNANE X RECEPTOR; PROTEIN C; WARFARIN;

ADULT; AGE; AGED; ANTICOAGULATION; ARTICLE; BLEEDING; BODY WEIGHT; CONTROLLED STUDY; DISEASE SEVERITY; DRUG EFFICACY; DRUG INDICATION; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TRANSFORMATION; FEMALE; GENE LINKAGE DISEQUILIBRIUM; GENOTYPE; HAPLOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; MULTIPLE REGRESSION; PHARMACOGENETICS; PRACTICE GUIDELINE; PREDICTION; PRESCRIPTION; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN POLYMORPHISM; RISK ASSESSMENT; SINGLE NUCLEOTIDE POLYMORPHISM; THROMBOEMBOLISM; VALIDATION PROCESS;

ADULT; AGED; AGED, 80 AND OVER; ANTICOAGULANTS; BIOSYNTHETIC PATHWAYS; CHROMOSOME MAPPING; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GENETIC MARKERS; HUMANS; MALE; MIDDLE AGED; MODELS, GENETIC; MULTIGENE FAMILY; WARFARIN;

EID: 33947227273     PISSN: 03406717     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00439-006-0260-8     Document Type: Article

References (69)

1. Aiach M, Nicaud V, Alhenc-Gelas M, Gandrille S, Arnaud E, Amiral J, Guize L, Fiessinger JN, Emmerich J (1999) Complex association of protein C gene promoter polymorphism with circulating protein C levels and thrombotic risk. Arterioscler Thromb Vasc Biol 19:1573-1576
2. Aquilante CL, Langaee TY, Lopez LM, Yarandi HN, Tromberg JS, Mohuczy D, Gaston KL, Waddell CD, Chirico MJ, Johnson JA (2006) Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements. Clin Pharmacol Ther 79:291-302
3. Arbini AA, Bodkin D, Lopaciuk S, Bauer KA (1994) Molecular analysis of Polish patients with factor VII deficiency. Blood 84:2214-2220
4. Bell RG, Sadowski JA, Matschiner JT (1972) Mechanism of action of warfarin. Warfarin and metabolism of vitamin K 1. Biochemistry 11:1959-1961
5. Berkner KL (2000) The vitamin K-dependent carboxylase. J Nutr 130:1877-1880
6. Berkner KL, Runge KW (2004) The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis. J Thromb Haemost 2:2118-2132
7. Bodin L, Verstuyft C, Tregouet DA, Robert A, Dubert L, Funck-Brentano C, Jaillon P, Beaune P, Laurent-Puig P, Becquemont L, Loriot MA (2005) Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood 106:135-140
8. Cain D, Hutson SM, Wallin R (1997) Assembly of the warfarin-sensitive vitamin K 2,3-epoxide reductase enzyme complex in the endoplasmic reticulum membrane. J Biol Chem 272:29068-29075
9. Chen LY, Eriksson N, Gwilliam R, Bentley D, Deloukas P, Wadelius M (2005) Gamma-glutamyl carboxylase (GGCX) microsatellite and warfarin dosing. Blood 106:3673-3674
10. Chen Y, Ferguson SS, Negishi M, Goldstein JA (2004) Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor. J Pharmacol Exp Ther 308:495-501
11. Cheverud JM (2001) A simple correction for multiple comparisons in interval mapping genome scans. Heredity 87:52-58
12. Dahlbäck B (2005) Blood coagulation and its regulation by anticoagulant pathways: Genetic pathogenesis of bleeding and thrombotic diseases. J Intern Med 257:209-223
13. Daly AK, King BP (2003) Pharmacogenetics of oral anticoagulants. Pharmacogenetics 13:247-252
14. D'Ambrosio RL, D'Andrea G, Cappucci F, Chetta M, Di Perna P, Brancaccio V, Grandone E, Margaglione M (2004) Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin. Haematologica 89:1510-1516
15. D'Andrea G, D'Ambrosio RL, Di Perna P, Chetta M, Santacroce R, Brancaccio V, Grandone E, Margaglione M (2005) A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 105:645-649
16. Dudbridge F (2003) Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 25:115-121
17. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296:2225-2229
18. Geick A, Eichelbaum M, Burk O (2001) Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem 276:14581-14587
19. Geisen C, Watzka M, Sittinger K, Steffens M, Daugela L, Seifried E, Muller CR, Wienker TF, Oldenburg J (2005) VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation. Thromb Haemost 94:773-779
20. Haining RL, Hunter AP, Veronese ME, Trager WF, Rettie AE (1996) Allelic variants of human cytochrome P450 2C9: Baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms. Arch Biochem Biophys 333:447-458
21. Huang W, Lin YS, McConn DJ II, Calamia JC, Totah RA, Isoherranen N, Glodowski M, Thummel KE (2004) Evidence of significant contribution from CYP3A5 to hepatic drug metabolism. Drug Metab Dispos 32:1434-1445
22. Kaminsky L, Zhang Z (1997) Human P450 metabolism of warfarin. Pharmacol Ther 73:67-74
23. Kohlmeier M, Salomon A, Saupe J, Shearer MJ (1996) Transport of vitamin K to bone in humans. J Nutr 126:1192S-1196S
24. Kohnke H, Scordo MG, Pengo V, Padrini R, Wadelius M (2005a) Apolipoprotein E (APOE) and warfarin dosing in an Italian population. Eur J Clin Pharmacol 61:781-783
25. Kohnke H, Sörlin K, Granath G, Wadelius M (2005b) Warfarin dose related to apolipoprotein E (APOE) genotype. Eur J Clin Pharmacol 61:381-388
26. Kristensen SR (2002) Warfarin treatment of a patient with coagulation factor IX propeptide mutation causing warfarin hypersensitivity. Blood 100:2676-2677
27. Landefeld C, Beyth R (1993) Anticoagulant-related bleeding: Clinical epidemiology, prediction and prevention. Am J Med 95:315-328
28. Larsen TB, Lassen JF, Dahler-Eriksen BS, Petersen PH, Brandslund I (1998) Effect of anticoagulant therapy on the hypercoagulable state in patients carrying the factor V Arg506Gln mutation. Thromb Res 92:157-162
29. Lee SC, Ng SS, Oldenburg J, Chong PY, Rost S, Guo JY, Yap HL, Rankin SC, Khor HB, Yeo TC, Ng KS, Soong R, Goh BC (2006) Interethnic variability of warfarin maintenance requirement is explained by VKORC1 genotype in an Asian population. Clin Pharmacol Ther 79:197-205
30. Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA (1998) The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J Clin Invest 102:1016-1023
31. Li H (2001) A permutation procedure for the haplotype method for identification of disease-predisposing variants. Ann Hum Genet 65:189-196
32. Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW (2004) Identification of the gene for vitamin K epoxide reductase. Nature 427:541-544
33. Loebstein R, Vecsler M, Kurnik D, Austerweil N, Gak E, Halkin H, Almog S (2005) Common genetic variants of microsomal epoxide hydrolase affect warfarin dose requirements beyond the effect of cytochrome P450 2C9. Clin Pharmacol Ther 77:365-372
34. Loebstein R, Yonath H, Peleg D, Almog S, Rotenberg M, Lubetsky A, et al (2001) Interindividual variability in sensitivity to warfarin- Nature or nurture? Clin Pharmacol Ther 70:159-164
35. McGinnis R, Wadelius M, Chen LY, Eriksson N, Deloukas P (2006) Search for additional genetic determinants of warfarin dose. In: European Mathematical Genetics Meeting (abstract 20) Cardiff, Wales, 6-7 April
36. Morisseau C, Hammock BD (2005) Epoxide hydrolases: Mechanisms, inhibitor designs, and biological roles. Annu Rev Pharmacol Toxicol 45:311-333
37. Nyholt DR (2004) A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74:765-769
38. Otagiri M, Maruyama T, Imai T, Suenaga A, Imamura Y (1987) A comparative study of the interaction of warfarin with human alpha 1-acid glycoprotein and human albumin. J Pharm Pharmacol 39:416-420
39. Palareti G, Legnani C (1996) Warfarin withdrawal. Pharmacokinetic-pharmacodynamic considerations. Clin Pharmacokinet 30:300-313
40. Pritchard JK, Przeworski M (2001) Linkage disequilibrium in humans: models and data. Am J Hum Genet 69:1-14
41. Rettie AE, Korzekwa KR, Kunze KL, Lawrence RF, Eddy AC, Aoyama T, Gelboin HV, Gonzalez FJ, Trager WF (1992) Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: A role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol 5:54-59
42. Rettie AE, Wienkers LC, Gonzalez FJ, Trager WF, Korzekwa KR (1994) Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics 4:39-42
43. Rieder MJ, Reiner AP, Gage BF, Nickerson DA, Eby CS, McLeod HL, Blough DK, Thummel KE, Veenstra DL, Rettie AE (2005) Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med 352:2285-2293
44. Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J (2004) Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 427:537-541
45. Sanderson S, Emery J, Higgins J (2005) CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: A HuGEnet systematic review and meta-analysis. Genet Med 7:97-104
46. Saupe J, Shearer MJ, Kohlmeier M (1993) Phylloquinone transport and its influence on gamma-carboxyglutamate residues of osteocalcin in patients on maintenance hemodialysis. Am J Clin Nutr 58:204-208
47. Sconce EA, Khan TI, Wynne HA, Avery P, Monkhouse L, King BP, Wood P, Kesteven P, Daly AK, Kamali F (2005) The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: Proposal for a new dosing regimen. Blood 106:2329-2333
48. Scordo MG, Pengo V, Spina E, Dahl ML, Gusella M, Padrini R (2002) Influence of CYP2C9 and CYP2C19 genetic polymorphisms on warfarin maintenance dose and metabolic clearance. Clin Pharmacol Ther 72:702-710
49. Shikata E, Ieiri I, Ishiguro S, Aono H, Inoue K, Koide T, Ohgi S, Otsubo K (2004) Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity. Blood 103:2630-2635
50. Spek CA, Koster T, Rosendaal FR, Bertina RM, Reitsma PH (1995) Genotypic variation in the promoter region of the protein C gene is associated with plasma protein C levels and thrombotic risk. Arterioscler Thromb vasc Bol 15:214-218
51. Sussman N, Waltershied M, Butler T, Cali J, Riss T, Kelly J (2002) The predictice nature of high throughput toxicity screening using a human hepatocyte cell line. Cell Notes 3:7-10
52. Takahashi H, Echizen H (2003) Pharmacogenetics of CYP2C9 and interindividual variability in anticoagulant response to warfarin. Pharmacogenomics J 3:202-214
53. Takahashi H, Kashima T, Nomizo Y, Muramoto N, Shimizu T, Nasu K, Kubota T, Kimura S, Echizen H (1998) Metabolism of warfarin enantiomers in Japanese patients with heart disease having different CYP2C9 and CYP2C19 genotypes. Clin Pharmacol Ther 63:519-528
54. Takahashi H, Wilkinson GR, Nutescu EA, Morita T, Ritchie MD, Scordo MG, Pengo V, Barban M, Padrini R, Ieiri I, Otsubo K, Kashima T, Kimura S, Kijima S, Echizen H (2006) 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 16:101-110
55. van der Heijden JF, Rekke B, Hutten BA, van der Meer FJ, Remkes MG, Vermeulen M, Buller HR, Reitsma PH (2004) Non-fatal major bleeding during treatment with vitamin K antagonists: Influence of soluble thrombomodulin and mutations in the propeptide of coagulation factor IX. J Thromb Haemost 2:1104-1109
56. Vecsler M, Loebstein R, Almog S, Kurnik D, Goldman B, Halkin H, Gak E (2006) Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin. Thromb Haemost 95:205-211
57. Veenstra DL, You JH, Rieder MJ, Farin FM, Wilkerson HW, Blough DK, Cheng G, Rettie AE (2005) Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population. Pharmacogenet Genomics 15:687-691
58. Visser LE, Trienekens PH, De Smet PA, Vulto AG, Hofman A, van Duijn CM, Stricker BH (2005) Patients with an ApoE epsilon4 allele require lower doses of coumarin anticoagulants. Pharmacogenet Genomics 15:69-74
59. Wadelius M, Pirmohamed M (2006) Pharmacogenetics of warfarin: Current status and future challenges. Pharmacogenomics. J (in press)
60. Wadelius M, Chen LY, Downes K, Ghori J, Hunt S, Eriksson N, Wallerman O, Melhus H, Wadelius C, Bentley D, Deloukas P (2005) Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Pharmacogenomics J 5:262-270
61. Wadelius M, Sörlin K, Wallerman O, Karlsson J, Yue QY, Magnusson PK, Wadelius C, Melhus H (2004) Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. Pharmacogenomics J 4:40-48
62. Wajih N, Sane DC, Hutson SM, Wallin R (2004) The inhibitory effect of calumenin on the vitamin K-dependent gamma-carboxylation system. Characterization of the system in normal and warfarin-resistant rats. J Biol Chem 279:25276-25283
63. Wallin R, Hutson S (1982) Vitamin K-dependent carboxylation. Evidence that at least two microsomal dehydrogenases reduce vitamin K1 to support carboxylation. J Biol Chem 257:1583-1586
64. Wallin R, Hutson SM, Cain D, Sweatt A, Sane DC (2001) A molecular mechanism for genetic warfarin resistance in the rat. Faseb J 15:2542-2544
65. Watala C, Golanski J, Kardas P (2003) Multivariate relationships between international normalized ratio and vitamin K-dependent coagulation-derived parameters in normal healthy donors and oral anticoagulant therapy patients. Thromb J 1:7
66. Whittaker P, Bumpstead S, Downes K, Ghori J, Deloukas P (2006) Single Nucleotide Polymorphism analysis by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry. In: Celis J (ed) Cell biology: A laboratory handbook, 3rd edn. Elsevier, Amsterdam
67. Wu SM, Stafford DW, Frazier LD, Fu YY, High KA, Chu K, Sanchez-Vega B, Solera J (1997) Genomic sequence and transcription start site for the human gamma-glutamyl carboxylase. Blood 89:4058-4062
68. Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Charng MJ, Lu MJ, Hung CR, Wei CY, Chen CH, Wu JY, Chen YT (2005) A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. Hum Mol Genet 14:1745-1751
69. Zhang Z, Fasco MJ, Huang Z, Guengerich FP, Kaminsky LS (1995) Human cytochromes P4501A1 and P4501A2: R-warfarin metabolism as a probe. Drug Metab Dispos 23:1339-1346