Identification of cytochrome P450 oxidoreductase gene variants that are significantly associated with the interindividual variations in warfarin maintenance dose

Drug Metabolism and Disposition

Volumn 39, Issue 8, 2011, Pages 1433-1439

  Zhang, Xiuling ^a   Li, Lei ^a   Ding, Xinxin ^a   Kaminsky, Laurence S ^b  

^a WADSWORTH CENTER   (United States)

^b STRATTON VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; CYTOCHROME P450 2C9; GENOMIC DNA; OXIDOREDUCTASE; UNCLASSIFIED DRUG; VITAMIN K EPOXIDE REDUCTASE COMPLEX SUBUNIT 1; WARFARIN;

ADULT; AGE DISTRIBUTION; AGED; ANTICOAGULANT THERAPY; ARTICLE; CONTROLLED STUDY; CYTOCHROME P450 OXIDOREDUCTASE GENE; DNA FLANKING REGION; DNA ISOLATION; DNA SEQUENCE; DOSE RESPONSE; DRUG METABOLISM; GENE; GENE FREQUENCY; GENE IDENTIFICATION; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; LONG TERM CARE; MAINTENANCE DRUG DOSE; MAJOR CLINICAL STUDY; MALE; NUCLEIC ACID BASE SUBSTITUTION; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; AGED; AGED, 80 AND OVER; ANTICOAGULANTS; ARYL HYDROCARBON HYDROXYLASES; ASPIRIN; CYTOCHROME P-450 ENZYME SYSTEM; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE FREQUENCY; GENOTYPE; HUMANS; INDIVIDUALIZED MEDICINE; LINEAR MODELS; MALE; MIDDLE AGED; MIXED FUNCTION OXYGENASES; MULTIPLEX POLYMERASE CHAIN REACTION; POLYMORPHISM, SINGLE NUCLEOTIDE; WARFARIN;

EID: 79960616137     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.038836     Document Type: Article

References (40)

1. Agrawal V, Choi JH, Giacomini KM, and Miller WL (2010) Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase. Pharmacogenet Genomics 20:611-618.
2. Aquilante CL, Langaee TY, Lopez LM, Yarandi HN, Tromberg JS, Mohuczy D, Gaston KL, Waddell CD, Chirico MJ, and 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. Arlt W, Walker EA, Draper N, Ivison HE, Ride JP, Hammer F, Chalder SM, Borucka-Mankiewicz M, Hauffa BP, Malunowicz EM, et al. (2004) Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study. Lancet 363:2128-2135. (Pubitemid 38844154)
4. Borgiani P, Ciccacci C, Forte V, Sirianni E, Novelli L, Bramanti P, and Novelli G (2009) CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population. Pharmacogenomics 10:261-266.
5. Caldwell MD, Awad T, Johnson JA, Gage BF, Falkowski M, Gardina P, Hubbard J, Turpaz Y, Langaee TY, Eby C, et al. (2008) CYP4F2 genetic variant alters required warfarin dose. Blood 111:4106-4112.
6. Chen CY and Schwartz RJ (1995) Identification of novel DNA binding targets and regulatory domains of a murine tinman homeodomain factor, nkx-2.5. J Biol Chem 270:15628-15633.
7. Cheng C, Kacherovsky N, Dombek KM, Camier S, Thukral SK, Rhim E, and Young ET (1994) Identification of potential target genes for Adr1p through characterization of essential nucleotides in UAS1. Mol Cell Biol 14:3842-3852. (Pubitemid 24160791)
8. Flück CE, Mullis PE, and Pandey AV (2010) Reduction in hepatic drug metabolizing CYP3A4 activities caused by P450 oxidoreductase mutations identified in patients with disordered steroid metabolism. Biochem Biophys Res Commun 401:149-153.
9. Flück CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF, Jabs EW, Mendonça BB, Fujieda K, and Miller WL (2004) Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet 36:228-230. (Pubitemid 38282745)
10. Gomes AM, Winter S, Klein K, Turpeinen M, Schaeffeler E, Schwab M, and Zanger UM (2009) Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation. Pharmacogenomics 10:579-599.
11. Gomes LG, Huang N, Agrawal V, Mendonça BB, Bachega TA, and Miller WL (2008) The common P450 oxidoreductase variant A503V is not a modifier gene for 21-hydroxylase deficiency. J Clin Endocrinol Metab 93:2913-2916. (Pubitemid 352008571)
12. Gu J, Weng Y, Zhang QY, Cui H, Behr M, Wu L, Yang W, Zhang L, and Ding X (2003) Liver-specific deletion of the NADPH-cytochrome P450 reductase gene: impact on plasma cholesterol homeostasis and the function and regulation of microsomal cytochrome P450 and heme oxygenase. J Biol Chem 278:25895-25901. (Pubitemid 36835351)
13. Guengerich FP (2008) Cytochrome p450 and chemical toxicology. Chem Res Toxicol 21:70-83.
14. Harada T, Ariyoshi N, Shimura H, Sato Y, Yokoyama I, Takahashi K, Yamagata S, Imamaki M, Kobayashi Y, Ishii I, et al. (2010) Application of Akaike information criterion to evaluate warfarin dosing algorithm. Thromb Res 126:183-190.
15. Hart SN, Wang S, Nakamoto K, Wesselman C, Li Y, and Zhong XB (2008) Genetic polymorphisms in cytochrome P450 oxidoreductase influence microsomal P450-catalyzed drug metabolism. Pharmacogenet Genomics 18:11-24. (Pubitemid 351161645)
16. Heinemeyer T, Wingender E, Reuter I, Hermjakob H, Kel AE, Kel OV, Ignatieva EV, Ananko EA, Podkolodnaya OA, Kolpakov FA, et al. (1998) Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Res 26:362-367. (Pubitemid 28295292)
17. Henderson CJ, Otto DM, Carrie D, Magnuson MA, McLaren AW, Rosewell I, and Wolf CR (2003) Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase. J Biol Chem 278:13480-13486. (Pubitemid 36800122)
18. Huang N, Agrawal V, Giacomini KM, and Miller WL (2008) Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations. Proc Natl Acad Sci USA 105:1733-1738. (Pubitemid 351346583)
19. Huang N, Pandey AV, Agrawal V, Reardon W, Lapunzina PD, Mowat D, Jabs EW, Van Vliet G, Sack J, Flück CE, et al. (2005) Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am J Hum Genet 76:729-749. (Pubitemid 40563096)
20. Kaminsky LS, Dunbar DA, Wang PP, Beaune P, Larrey D, Guengerich FP, Schnellmann RG, and Sipes IG (1984) Human hepatic cytochrome P-450 composition as probed by in vitro microsomal metabolism of warfarin. Drug Metab Dispos 12:470-477. (Pubitemid 14091824)
21. Limdi NA and Veenstra DL (2008) Warfarin pharmacogenetics. Pharmacotherapy 28:1084-1097.
22. Marohnic CC, Panda SP, McCammon K, Rueff J, Masters BS, and KranendonkM(2010) Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. Drug Metab Dispos 38:332-340.
23. Marsh S and McLeod HL (2006) Pharmacogenomics: from bedside to clinical practice. Hum Mol Genet 15 (Spec No 1):R89-R93.
24. Miller WL, Agrawal V, Sandee D, Tee MK, Huang N, Choi JH, Morrissey K, and Giacomini KM (2011) Consequences of POR mutations and polymorphisms. Mol Cell Endocrinol 336:174-179.
25. Miller WL, Huang N, Agrawal V, and Giacomini KM (2009) Genetic variation in human P450 oxidoreductase. Mol Cell Endocrinol 300:180-184.
26. Nicolo C, Flück CE, Mullis PE, and Pandey AV (2010) Restoration of mutant cytochrome P450 reductase activity by external flavin. Mol Cell Endocrinol 321:245-252.
27. Oneda B, Crettol S, Jaquenoud Sirot E, Bochud M, Ansermot N, and Eap CB (2009) The P450 oxidoreductase genotype is associated with CYP3A activity in vivo as measured by the midazolam phenotyping test. Pharmacogenet Genomics 19:877-883.
28. Porter TD and Coon MJ (1991) Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J Biol Chem 266:13469-13472. (Pubitemid 21907368)
29. Rettie AE and Tai G (2006) The pharmacogenomics of warfarin: closing in on personalized medicine. Mol Interv 6:223-227. (Pubitemid 44455204)
30. Sandee D, Morrissey K, Agrawal V, Tam HK, Kramer MA, Tracy TS, Giacomini KM, and Miller WL (2010) Effects of genetic variants of human P450 oxidoreductase on catalysis by CYP2D6 in vitro. Pharmacogenet Genomics 20:677-686.
31. Schadt EE, Molony C, Chudin E, Hao K, Yang X, Lum PY, Kasarskis A, Zhang B, Wang S, Suver C, et al. (2008) Mapping the genetic architecture of gene expression in human liver. PLoS Biol 6:e107.
32. Schelleman H, Limdi NA, and Kimmel SE (2008) Ethnic differences in warfarin maintenance dose requirement and its relationship with genetics. Pharmacogenomics 9:1331-1346.
33. Sim SC, Miller WL, Zhong XB, Arlt W, Ogata T, Ding X, Wolf CR, Flück CE, Pandey AV, Henderson CJ, et al. (2009) Nomenclature for alleles of the cytochrome P450 oxidoreductase gene. Pharmacogenet Genomics 19:565-566.
34. Singh O, Sandanaraj E, Subramanian K, Lee LH, and Chowbay B (2011) Influence of CYP4F2 rs2108622 (V433M) on warfarin dose requirement in Asian patients. Drug Metab Pharmacokinet 26:130-136.
35. Takeuchi F, McGinnis R, Bourgeois S, Barnes C, Eriksson N, Soranzo N, Whittaker P, Ranganath V, Kumanduri V, McLaren W, et al. (2009) A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet 5:e1000433.
36. Tee MK, Huang N, Damm I, and Miller WL (2011) Transcriptional regulation of the human P450 oxidoreductase gene: hormonal regulation and influence of promoter polymorphisms. Mol Endocrinol 25:715-731.
37. Tomalik-Scharte D, Maiter D, Kirchheiner J, Ivison HE, Fuhr U, and Arlt W (2010) Impaired hepatic drug and steroid metabolism in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency. Eur J Endocrinol 163:919-924.
38. Wadelius M and Pirmohamed M (2007) Pharmacogenetics of warfarin: current status and future challenges. Pharmacogenomics J 7:99-111. (Pubitemid 46567142)
39. Yin T and Miyata T (2007) Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1-rationale and perspectives. Thromb Res 120:1-10. (Pubitemid 46601582)
40. Zhang QY, Fang C, Zhang J, Dunbar D, Kaminsky L, and Ding X (2009) An intestinal epithelium-specific cytochrome P450 (P450) reductase-knockout mouse model: direct evidence for a role of intestinal P450s in first-pass clearance of oral nifedipine. Drug Metab Dispos 37:651-657.