CYP2C9

Summary

Gene Symbol: CYP2C9
Description: cytochrome P450 family 2 subfamily C member 9
Alias: CPC9, CYP2C, CYP2C10, CYPIIC9, P450IIC9, cytochrome P450 2C9, cytochrome P-450 S-mephenytoin 4-hydroxylase, cytochrome P-450MP, cytochrome P450 PB-1, cytochrome P450, family 2, subfamily C, polypeptide 9, flavoprotein-linked monooxygenase, microsomal monooxygenase, xenobiotic monooxygenase
Species: human

Top Publications

  1. ncbi The frequency and effects of cytochrome P450 (CYP) 2C9 polymorphisms in patients receiving warfarin
    Arash Rafii Tabrizi
    Department of Surgery, Washington University School of Medicine, St Louis, MO, 63110, USA
    J Am Coll Surg 194:267-73. 2002
  2. ncbi A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity
    Hsiang Yu Yuan
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
    Hum Mol Genet 14:1745-51. 2005
  3. pmc A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose
    Fumihiko Takeuchi
    Wellcome Trust Sanger Institute, Hinxton, UK
    PLoS Genet 5:e1000433. 2009
  4. ncbi The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen
    Elizabeth A Sconce
    School of Clinical and Laboratory Sciences, University of Newcastle, Newcastle upon Tyne, United Kingdom
    Blood 106:2329-33. 2005
  5. ncbi Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention
    Wade S Samowitz
    Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
    Clin Gastroenterol Hepatol 4:894-901. 2006
  6. ncbi Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study
    John F Carlquist
    Department of Medicine, Division of Cardiology, University of Utah School of Medicine, Cardiovascular Department, LDS Hospital, Salt Lake City, Utah, USA
    J Thromb Thrombolysis 22:191-7. 2006
  7. ncbi Crystal structure of human cytochrome P450 2C9 with bound warfarin
    Pamela A Williams
    Astex Technology, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK
    Nature 424:464-8. 2003
  8. doi CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population
    Paola Borgiani
    Department of Biopathology and Diagnostic Imaging, School of Medicine, Tor Vergata University, Rome, Italy
    Pharmacogenomics 10:261-6. 2009
  9. pmc Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a black African population
    M G Scordo
    Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology at Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden
    Br J Clin Pharmacol 52:447-50. 2001
  10. pmc Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation
    T Li
    University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    J Med Genet 43:740-4. 2006

Research Grants

  1. Pharmacogenetics of ADRs: Warfarin Toxicity
    ALLAN EDWARD RETTIE; Fiscal Year: 2010
  2. Nita A Limdi; Fiscal Year: 2016
  3. Pharmacogenetic Optimization of Analgesic Prescribing in Sickle Cell Disease
    Cheedy Jaja; Fiscal Year: 2013
  4. Pharmacogenetics and Drug Interactions
    Richard C Brundage; Fiscal Year: 2012
  5. NOVEL HIGH THROUGHPUT PLATFORM FOR SCREENING CYTOCHROME P450 INDUCTION
    MARIA INES MORANO; Fiscal Year: 2013
  6. Comprehensive studies of novel SNPs affecting warfarin dose in African Americans
    Minoli Perera; Fiscal Year: 2012
  7. The implementation of a pharmacogenomics-based algorithm for warfarin dosing
    Minoli Perera; Fiscal Year: 2013
  8. Personalized medicine informatics for anticoagulation therapy
    Roland Valdes; Fiscal Year: 2012
  9. Cytochrome P450 Eicosanoids and Myocardial Injury
    GARRETT JOHN GROSS; Fiscal Year: 2012
  10. Paul R Ortiz de Montellano; Fiscal Year: 2014

Detail Information

Publications265 found, 100 shown here

  1. ncbi The frequency and effects of cytochrome P450 (CYP) 2C9 polymorphisms in patients receiving warfarin
    Arash Rafii Tabrizi
    Department of Surgery, Washington University School of Medicine, St Louis, MO, 63110, USA
    J Am Coll Surg 194:267-73. 2002
    ..to warfarin therapy, we determined the frequency and functional effects of polymorphisms of the predominant cytochrome P450 subfamily responsible for warfarin metabolism (eg, CYP2C9) in an ethnically defined U.S. patient population.
  2. ncbi A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity
    Hsiang Yu Yuan
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
    Hum Mol Genet 14:1745-51. 2005
    ..We determined DNA sequence variants in CYP2C9 and VKORC1 in 16 Chinese patients having warfarin sensitivity (< or = 1...
  3. pmc A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose
    Fumihiko Takeuchi
    Wellcome Trust Sanger Institute, Hinxton, UK
    PLoS Genet 5:e1000433. 2009
    ..another approximately 12% by two non-synonymous SNPs (*2, *3) in the cytochrome P450 warfarin-metabolizing gene CYP2C9. We initially tested each of 325,997 GWAS SNPs for association with warfarin dose by univariate regression and ..
  4. ncbi The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen
    Elizabeth A Sconce
    School of Clinical and Laboratory Sciences, University of Newcastle, Newcastle upon Tyne, United Kingdom
    Blood 106:2329-33. 2005
    ..This study investigated the contribution of age, CYP2C9 and VKORC1 genotype, and body size to warfarin-dose requirements...
  5. ncbi Interactions between CYP2C9 and UGT1A6 polymorphisms and nonsteroidal anti-inflammatory drugs in colorectal cancer prevention
    Wade S Samowitz
    Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
    Clin Gastroenterol Hepatol 4:894-901. 2006
    ..between UGT1A6 variants or variants of another enzyme that metabolizes nonsteroidal anti-inflammatory drugs (NSAIDs), cytochrome P4502C9 (CYP2C9), and NSAIDs in the prevention of colorectal cancer have not been studied extensively.
  6. ncbi Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study
    John F Carlquist
    Department of Medicine, Division of Cardiology, University of Utah School of Medicine, Cardiovascular Department, LDS Hospital, Salt Lake City, Utah, USA
    J Thromb Thrombolysis 22:191-7. 2006
    ..e., CYP2C9) and activity (i.e., vitamin K epoxide reductase complex subunit 1-VKORC1)...
  7. ncbi Crystal structure of human cytochrome P450 2C9 with bound warfarin
    Pamela A Williams
    Astex Technology, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK
    Nature 424:464-8. 2003
    ..Human CYP450 proteins CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the major drug-metabolizing isoforms, and contribute to the oxidative metabolism ..
  8. doi CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population
    Paola Borgiani
    Department of Biopathology and Diagnostic Imaging, School of Medicine, Tor Vergata University, Rome, Italy
    Pharmacogenomics 10:261-6. 2009
    ..Numerous papers have shown the important contribution of CYP2C9 and VKORC1 genetic variants to this variability...
  9. pmc Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a black African population
    M G Scordo
    Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology at Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden
    Br J Clin Pharmacol 52:447-50. 2001
    b>CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect the therapeutic outcome during treatment with several drugs...
  10. pmc Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage requirements in patients receiving anticoagulation
    T Li
    University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    J Med Genet 43:740-4. 2006
    ..However, the use of this common agent is fraught with complications and little is known regarding inter-individual variation in warfarin response...
  11. ncbi Contribution of age, body weight, and CYP2C9 and VKORC1 genotype to the anticoagulant response to warfarin: proposal for a new dosing regimen in Chinese patients
    Liyan Miao
    Department of Clinical Pharmacology Research Lab, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
    Eur J Clin Pharmacol 63:1135-41. 2007
    The objective of this study was to assess the contribution of the VKORC1 and CYP2C9 genotypes and age, body size, and weight of the patients to the warfarin dose requirement in a Chinese population.
  12. ncbi Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms
    Chin Chuan Hung
    Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
    Ther Drug Monit 26:534-40. 2004
    To search for the optimal dosage of phenytoin in patients with epilepsy based on the metabolic activities of CYP2C9 and CYP2C19 polymorphisms, a total of 169 patients receiving phenytoin treatment for more than 1 month were recruited...
  13. pmc Intramolecular heme ligation of the cytochrome P450 2C9 R108H mutant demonstrates pronounced conformational flexibility of the B-C loop region: implications for substrate binding
    Arthur G Roberts
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, USA
    Biochemistry 49:8700-8. 2010
    ..et al. (2004) Mol. Pharmacol. 65, 842-850] revealed some unusual properties of the R108H mutant of cytochrome P450 2C9 (CYP2C9), including elevated thermostability relative to that of CYP2C9, as well as a UV-visible absorbance ..
  14. ncbi Biochemistry and molecular biology of the human CYP2C subfamily
    J A Goldstein
    National Institutes of Environmental Health Sciences, Research Triangle Park, NC 27709
    Pharmacogenetics 4:285-99. 1994
    ..Four members of this subfamily have been identified in humans: CYP2C8, CYP2C9, CYP2C18, and CYP2C19...
  15. ncbi Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2 and of P-glycoprotein in a Russian population
    Elena A Gaikovitch
    Institute of Clinical Pharmacology, University Clinic Charite, Humboldt University of Berlin, Schumannstrasse 20 21, 10098 Berlin, Germany
    Eur J Clin Pharmacol 59:303-12. 2003
    ..However, little is known of the frequency distribution of the major allelic variants in the Russian population...
  16. ncbi The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement
    J van der Weide
    Department of Clinical Chemistry, St Jansdal Hospital, Harderwijk, The Netherlands
    Pharmacogenetics 11:287-91. 2001
    The cytochrome P450 enzyme CYP2C9 catalyses the metabolism of numerous therapeutic agents, including the anti-epileptic drug phenytoin...
  17. ncbi CYP2C9 allelic variants: ethnic distribution and functional significance
    Hong Guang Xie
    Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 6602, USA
    Adv Drug Deliv Rev 54:1257-70. 2002
    Cytochrome P-450 (CYP) 2C9 CYP2C9 is a polymorphically expressed enzyme responsible for the metabolism of several clinically important drugs, some with a low therapeutic index...
  18. ncbi Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with warfarin sensitivity in Chinese patients
    A Y Leung
    Division of Haematology and Oncology, Department of Medicine, The University of Hong Kong
    Blood 98:2584-7. 2001
    b>CYP2C9 polymorphisms reported in Caucasians (Arg144Cys in exon 3 and Ile359Leu in exon 7) are extremely uncommon in Chinese persons...
  19. ncbi Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy
    Mitchell K Higashi
    University of Washington, Department of Pharmacy, Box 357630, Health Sciences Bldg, Room H 375A, Seattle, WA 98195, USA
    JAMA 287:1690-8. 2002
    ..The principal enzyme involved in warfarin metabolism is CYP2C9, and 2 relatively common variant forms with reduced activity have been identified, CYP2C9*2 and CYP2C9*3...
  20. ncbi Developmental expression of human hepatic CYP2C9 and CYP2C19
    Sevasti B Koukouritaki
    Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226 4801, USA
    J Pharmacol Exp Ther 308:965-74. 2004
    ..To determine developmental expression patterns, liver microsomal CYP2C9 and -2C19 were measured (n = 237; ages, 8 weeks gestation-18 years) by Western blotting and with diclofenac or ..
  21. ncbi Polymorphism in CYP2C9 as a non-critical factor of warfarin dosage adjustment in Korean patients
    Sukhyang Lee
    Graduate School of Clinical Pharmacy, Sookmyung Womens University, Seoul 140 742, Korea
    Arch Pharm Res 26:967-72. 2003
    Cytochrome P4502C9(CYP2C9) is largely responsible for terminating anticoagulant effect by hydroxylation of S-warfarin to inactive metabolites...
  22. ncbi The frequency of cytochrome P450 2C9 genetic variants in the Russian population and their associations with individual sensitivity to warfarin therapy
    Sofya N Pchelina
    Saint Petersburg Pavlov State Medical University, St Petersburg, Russia Petersburg Nuclear Physics Institute, St Petersburg, Russia
    Thromb Res 115:199-203. 2005
  23. pmc Impact of age, CYP2C9 genotype and concomitant medication on the rate of rise for prothrombin time during the first 30 days of warfarin therapy
    Russell A Wilke
    Department of Internal Medicine, Marshfield Clinic, WI 54449, USA
    Clin Med Res 3:207-13. 2005
    ..To characterize the impact of several important clinical variables on the rate of anticoagulation during warfarin initiation (i.e., the first 30 days)...
  24. pmc Association of warfarin dose with genes involved in its action and metabolism
    Mia Wadelius
    Department of Medical Sciences, Clinical Pharmacology, University Hospital, 751 85 Uppsala, Sweden
    Hum Genet 121:23-34. 2007
    ..In our study, polymorphisms in or flanking the genes VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, APOE, EPHX1, CALU, GGCX and ORM1-ORM2 and haplotypes of VKORC1, CYP2C9, CYP2C8, CYP2C19, ..
  25. ncbi Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients
    Rina Kimura
    Research Institute, Japan
    Thromb Res 120:181-6. 2007
    ..four genes, vitamin K epoxide reductase (VKORC1), gamma-glutamyl carboxylase (GGCX), calumenin (CALU), and cytochrome P450 2C9 (CYP2C9) to the warfarin maintenance dose required in Japanese patients following ischemic stroke...
  26. ncbi CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study
    Y Caraco
    Clinical Pharmacology Unit, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel
    Clin Pharmacol Ther 83:460-70. 2008
    Warfarin anticoagulation effect is characterized by marked variability, some of which has been attributed to CYP2C9 polymorphisms...
  27. ncbi CYP2C9 genotypes and the quality of anticoagulation control with warfarin therapy among Brazilian patients
    M V Lima
    Departamento de Medicina Clinica, Hospital Universitario Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, Brazil
    Eur J Clin Pharmacol 64:9-15. 2008
    To evaluate the impact of the two most common CYP2C9 variant alleles (*2 and *3) on the maintenance dose of warfarin and on the quality of anticoagulation control in Brazilians.
  28. pmc The largest prospective warfarin-treated cohort supports genetic forecasting
    Mia Wadelius
    Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden
    Blood 113:784-92. 2009
    Genetic variants of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) are known to influence warfarin dose, but the effect of other genes has not been fully elucidated...
  29. doi The role of CYP2C9 gene polymorphisms on anticoagulant therapy after heart valve replacement
    Hatice Yildirim
    Department of Biochemistry, Mersin University Faculty of Medicine, Mersin, Turkey
    Med Princ Pract 17:464-7. 2008
    The aim of the present study was to investigate the role of CYP2C9 gene polymorphisms after heart valve replacement in a group of patients on warfarin therapy.
  30. doi Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales
    Johanna Sistonen
    Department of Forensic Medicine, University of Helsinki, Helsinki, Finland
    Pharmacogenet Genomics 19:170-9. 2009
    b>CYP2C9, CYP2C19, and CYP2D6 belong to a subfamily of cytochrome P450 (CYP) enzymes, associated mainly with the metabolism of exogenous compounds in the human body...
  31. ncbi The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels
    R Kerb
    Epidauros Biotechnology AG, Pharmacogenetics Laboratory, Bernried, Germany
    Pharmacogenomics J 1:204-10. 2001
    ..differences in dose response can partially be explained by known genetic polymorphisms in the metabolic enzyme CYP2C9 but a large deal of individual variability remains still unexplained...
  32. doi Hepatic metabolism and transporter gene variants enhance response to rosuvastatin in patients with acute myocardial infarction: the GEOSTAT-1 Study
    Kristian M Bailey
    Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom
    Circ Cardiovasc Genet 3:276-85. 2010
    ..Pharmacogenetics aims to maximize benefits and minimize risks of drug treatment. Our objectives were to examine the influence of common variants of hepatic metabolism and transporter genes on the lipid-lowering response to statin therapy...
  33. pmc Allele and genotype frequencies of CYP2C9 in a Korean population
    Jung Woo Bae
    Laboratory of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon, Korea
    Br J Clin Pharmacol 60:418-22. 2005
    To determine the frequencies of the variant alleles and the genotypes of CYP2C9 in a Korean population.
  34. doi Genetic factors contribute to patient-specific warfarin dose for Han Chinese
    Ting Liang Wang
    Mochtar Riady Institute for Nanotechnology, Jl Boulevard Jend Sudirman, No 1688, Lippo Karawaci, Tangerang, Banten, Indonesia
    Clin Chim Acta 396:76-9. 2008
    ..To address the association of genetic factors and warfarin dosage for ethnic Han Chinese, we genotyped six candidate genes involved in the warfarin interactive pathway with focus on SNPs with reported association with warfarin dose...
  35. pmc Functional analysis of phenylalanine residues in the active site of cytochrome P450 2C9
    Carrie M Mosher
    Department of Medicinal Chemistry, University of Washington, Seattle, Washington 98195, USA
    Biochemistry 47:11725-34. 2008
    The two published crystal structures of cytochrome P450 2C9, complexed with ( S)-warfarin or flurbiprofen, implicate a cluster of three active site phenylalanine residues (F100, F114, F476) in ligand binding...
  36. ncbi CYP2C9 polymorphism: prevalence in healthy and warfarin-treated Malay and Chinese in Malaysia
    H A Ngow
    Department of Internal Medicine, Faculty of Medicine, International Islamic University Malaysia Hospital Tengku Ampuan Afzan, Jalan Istana, Bandar Indera Mahkota, Kuantan 25200, Malaysia
    Singapore Med J 50:490-3. 2009
    Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different...
  37. ncbi No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARdelta and PPARgamma act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma
    Louise E McGreavey
    Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee, UK
    Pharmacogenet Genomics 15:713-21. 2005
    ..Our objective was to investigate whether or not a number of the polymorphic genes involved in the metabolism of NSAIDs, including cytochrome P450 s (CYPs), act as modifiers of this protective effect...
  38. ncbi Estimation of warfarin maintenance dose based on VKORC1 (-1639 G>A) and CYP2C9 genotypes
    Yusheng Zhu
    Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA
    Clin Chem 53:1199-205. 2007
    b>CYP2C9 polymorphisms are associated with decreased S-warfarin clearance and lower maintenance dosage. Decreased expression of VKORC1 resulting from the -1639G>A substitution has also been implicated in lower warfarin dose requirements...
  39. ncbi The impact of CYP2C9 genetics and oral contraceptives on cytochrome P450 2C9 phenotype
    Mia Sandberg
    Division of Clinical Pharmacology, Karolinska University Hospital at Huddinge, SE 141 86 Stockholm, Sweden
    Drug Metab Dispos 32:484-9. 2004
    b>CYP2C9-dependent drug metabolism is subject to large interindividual variation. To some extent, this is explained by genetic polymorphism with expression of enzyme variants that differ in catalytic activity...
  40. ncbi Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes
    Werner Schroth
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Auerbachstrasse 112, D 70376 Stuttgart, Germany
    J Clin Oncol 25:5187-93. 2007
    ..We investigated the predictive value of genetic variants of CYP2D6, CYP2C19, and three other cytochrome P450 enzymes for tamoxifen treatment outcome...
  41. pmc Frequency of cytochrome P450 2C9 mutant alleles in a Korean population
    Y R Yoon
    Department of Pharmacology, Inje University College of Medicine and Clinical Pharmacology Center, Pusan Paik Hospital, Korea
    Br J Clin Pharmacol 51:277-80. 2001
    To determine the frequencies of CYP2C9 variants in the Korean population and compare them with the frequencies in other ethnic populations.
  42. ncbi Linkage between the CYP2C8 and CYP2C9 genetic polymorphisms
    Umit Yasar
    Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden
    Biochem Biophys Res Commun 299:25-8. 2002
    Cytochrome P450 (CYP) 2C8 and 2C9 are polymorphic enzymes. The CYP2C8*3 and CYP2C9*2 are the major variant alleles in Caucasian populations...
  43. pmc Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans
    Julia Kirchheiner
    Institute of Clinical Pharmacology, University Medical Centre Charité, Humboldt University, Berlin, Germany
    Br J Clin Pharmacol 55:51-61. 2003
    The cytochrome P450 enzyme CYP2C9 catalyses the 4'-hydroxylation of the nonsteroidal analgesic drug diclofenac in humans...
  44. pmc Genetic polymorphisms of CYP2C9 and CYP2C19 in the Beninese and Belgian populations
    Aurel C Allabi
    Medical Faculty of National University of Benin UNB, Applied Molecular Technologies, Centre for Human Genetics, Universite Catholique de Louvain UCL, Louvain, Belgium
    Br J Clin Pharmacol 56:653-7. 2003
    To investigate the distribution of cytochrome P450 2C9 (CYP2C9) and 2C19 (CYP2C19) genotype frequencies in the Beninese and Belgian Caucasian populations.
  45. ncbi Relative impact of covariates in prescribing warfarin according to CYP2C9 genotype
    Michael A Hillman
    Department of Care Management, Marshfield Clinic, Marshfield, Wisconsin, USA
    Pharmacogenetics 14:539-47. 2004
    ..Patients possessing variants (*2 and *3) of the cytochrome P450 2C9 gene require reduced maintenance doses compared to those having wild-type alleles (*1)...
  46. ncbi Prospective dosing of warfarin based on cytochrome P-450 2C9 genotype
    Deepak Voora
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Thromb Haemost 93:700-5. 2005
    Cytochrome P-450 2C9 (CYP2C9) polymorphisms (CYP2C9*2 and CYP2C9*3) reduce the clearance of warfarin, increase the risk of bleeding, and prolong the time to stable dosing...
  47. ncbi The Prevalence of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in African Americans with hypertension
    Albert W Dreisbach
    Divisions of Nephrology and Clinical Pharmacology, Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA
    Am J Hypertens 18:1276-81. 2005
    ..We performed a case-control study to determine the prevalence of epoxygenase-related SNP in African American individuals and to evaluate whether these SNP are associated with increased risk of hypertension...
  48. ncbi Interethnic and intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals
    Elena Garcia-Martin
    Department of Biochemistry and Molecular Biology, School of Sciences, University of Extremadura, Badajoz, Spain
    Mol Diagn Ther 10:29-40. 2006
    Cytochrome P450 (CYP) superfamily members CYP2C8 and CYP2C9 are polymorphically expressed enzymes that are involved in the metabolic inactivation of several drugs, including, among others, antiepileptics, NSAIDs, oral hypoglycemics, and ..
  49. ncbi The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement
    Darja Herman
    Institute of Biochemistry, Faculty of Medicine, Vrazov trg 2, SI 1000 Ljubljana, Slovenia
    Thromb Haemost 95:782-7. 2006
    ..dose required to achieve the desired anticoagulant response can only partly be explained by polymorphisms in the CYP2C9 gene, suggesting that additional genetic factors such as polymorphisms in genes involved in blood coagulation may ..
  50. ncbi Transcriptional activation of CYP2C9, CYP1A1, and CYP1A2 by hepatocyte nuclear factor 4alpha requires coactivators peroxisomal proliferator activated receptor-gamma coactivator 1alpha and steroid receptor coactivator 1
    Celia P Martinez-Jimenez
    Unidad de Hepatologia Experimental, Centro de Investigacion, Hospital La Fe, Avenida de Campanar, 21, 46009 Valencia, Spain
    Mol Pharmacol 70:1681-92. 2006
    ..Reporter assays with a chimeric CYP2C9-LUC construct demonstrated that the sole transfection of coactivators induced luciferase activity in HepG2 cells...
  51. ncbi CYP2C9 and VKORC1 genetic polymorphism analysis might be necessary in patients with Factor V Leiden and prothrombin gene G2021A mutation(s)
    Allen Leung
    Molecular Pathology Laboratory, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA
    Diagn Mol Pathol 16:184-6. 2007
    ..Patients with either Cytochrome P-450 CYP2C9*2, CYP2C9*3, or VKORC1*2 genotype (c...
  52. pmc Genetic determinants of response to warfarin during initial anticoagulation
    Ute I Schwarz
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, USA
    N Engl J Med 358:999-1008. 2008
    Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to various ..
  53. doi Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide
    Corine Ekhart
    Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute Slotervaart Hospital, Amsterdam, The Netherlands
    Pharmacogenet Genomics 18:515-23. 2008
    ..The purpose of this study was to evaluate the effects of known allelic variants in the CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1 genes on the pharmacokinetics of the anticancer agent, ..
  54. ncbi An analysis of the relative effects of VKORC1 and CYP2C9 variants on anticoagulation related outcomes in warfarin-treated patients
    Lisa M Meckley
    University of Washington, Department of Pharmacy, Seattle, WA 98195, USA
    Thromb Haemost 100:229-39. 2008
    The objective of this study was to assess the relative influence of VKORC1 and CYP2C9 genetic variants on several clinical outcomes related to warfarin treatment...
  55. ncbi 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
    R L Haining
    Department of Medicinal Chemistry, University of Washington, Seattle 98195, USA
    Arch Biochem Biophys 333:447-58. 1996
    The purpose of the present studies was to define the role of the I359L allelic variant of CYP2C9 in the metabolism of the low therapeutic index anticoagulant warfarin, by performing in vitro kinetic studies with the two enantiomers of the ..
  56. ncbi Genetic analysis of the human cytochrome P450 CYP2C9 locus
    M J Stubbins
    Biomedical Research Centre, University of Dundee, Ninewells Hospital, Tayside, UK
    Pharmacogenetics 6:429-39. 1996
    ..To date six different human CYP2C9 cDNA sequences, as well as the highly homologous CYP2C10 sequence have been reported suggesting that the CYP2C9 gene is polymorphic...
  57. ncbi Allelic and functional variability of cytochrome P4502C9
    C R Bhasker
    Department of Clinical Pharmacology, Flinders University of South Australia, Australia
    Pharmacogenetics 7:51-8. 1997
    ..nucleotide substitutions are known to result in a different amino acid at one of four sites in cytochrome P4502C9 (CYP2C9) namely: residue 144: Arg/Cys; residue 358: Tyr/Cys; residue 359: Ile/Leu and residue 417: Gly/Asp...
  58. pmc Cytochrome P4502C9: an enzyme of major importance in human drug metabolism
    J O Miners
    Department of Clinical Pharmacology, Flinders Medical Centre and Flinders University School of Medicine, Bedford Park, SA, Australia
    Br J Clin Pharmacol 45:525-38. 1998
    Accumulating evidence indicates that CYP2C9 ranks amongst the most important drug metabolizing enzymes in humans. Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S-warfarin, and numerous NSAIDs...
  59. ncbi Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients: genetic analysis of the CYP2C9 locus
    J Imai
    Division of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan
    Pharmacogenetics 10:85-9. 2000
  60. ncbi Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin
    R S Kidd
    Department of Biopharmaceutical Sciences, Bernard J Dunn School of Pharmacy, Shenandoah University, Winchester, VA 22601, USA
    Pharmacogenetics 11:803-8. 2001
    ..Two polymorphic alleles CYP2C9*2 and CYP2C9*3 have been documented which affect the metabolism and clinical toxicity of drugs such as phenytoin, ..
  61. pmc Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population
    Samar Ismail Hamdy
    Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan
    Br J Clin Pharmacol 53:596-603. 2002
    The goal of this study was to determine the frequencies of important allelic variants of CYP2C9, CYP2C19, CYP2E1 and DPYD in the Egyptian population and compare them with the frequencies in other ethnic populations.
  62. ncbi Genetic and environmental risk factors for oral anticoagulant overdose
    C Verstuyft
    Department of Pharmacology, Saint Antoine Paris VI University and Assistance Publique Hôpitaux de Paris, 184 rue du Faubourg Saint Antoine, 75012, Paris, France
    Eur J Clin Pharmacol 58:739-45. 2003
    b>Cytochrome P450 2C9 (CYP2C9) allelic variant carriers have been shown to experience hyper-responsiveness to small doses of oral anticoagulants (OAs) (warfarin or acenocoumarol) and a higher bleeding rate.
  63. ncbi Genetic polymorphisms of cytochromes P450: CYP2C9, CYP2C19, and CYP2D6 in Croatian population
    Nada Bozina
    University Institute of Laboratory Diagnosis, Zagreb University Hospital Center and School of Medicine, Zagreb, Croatia
    Croat Med J 44:425-8. 2003
    To determine the prevalence of most common mutations of cytochrome P450 (CYP), ie, allelic variants of CYP2C9, CYP2C19, and CYP2D6, and to predict genotype frequency in the Croatian population.
  64. ncbi Allelic variants of cytochromes P450 2C modify the risk for acute myocardial infarction
    Umit Yasar
    Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden
    Pharmacogenetics 13:715-20. 2003
    ..This study describes the relationship between genetic variants of CYP2C8 and CYP2C9, and morbidity in myocardial infarction in a large Swedish patient material...
  65. ncbi Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin
    Brian F Gage
    Department of Medicine, Washington University School of Medicine Campus Box 8005, 660 S Euclid Ave St Louis, Missouri 63110, USA
    Thromb Haemost 91:87-94. 2004
    ..Using polymerase chain reaction, we genotyped each participant for the presence of 8 polymorphisms in the cytochrome P450 2C9 system. Using multiple regression, we quantified the association between warfarin dose and all factors...
  66. ncbi 5'-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients
    Harumi Takahashi
    Department of Pharmacotherapy, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan
    Blood 103:3055-7. 2004
    ..therapeutic anticoagulation, but this can be only partly explained by genetic variability in the coding region of CYP2C9-a critical enzyme in the drug's metabolism. Accordingly, analysis of the -2...
  67. ncbi Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism
    Barry P King
    School of Clinical and Laboratory Sciences, University of Newcastle upon Tyne, Medical School, Newcastle upon Tyne, UK
    Pharmacogenetics 14:813-22. 2004
    To assess whether CYP2C9 alleles other than CYP2C9*2 and *3 are associated with a low-warfarin dose requirement and the relevance of upstream CYP2C9 polymorphisms to dose requirement and metabolism.
  68. ncbi CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis
    Simon Sanderson
    Department of Public Health and Primary Care, University of Cambridge and Cambridge Genetics Knowledge Park, Cambridge, UK
    Genet Med 7:97-104. 2005
    Two common variant alleles of the cytochrome CYP2C9 (CYP2C9*2 and CYP2C9*3) lead to reduced warfarin metabolism in vitro and in vivo...
  69. ncbi CYP2C9 haplotype structure in European American warfarin patients and association with clinical outcomes
    David L Veenstra
    Department of Pharmacy, Environmental Health, Genome Sciences, and Medicinal Chemistry, University of Washington, Seattle, USA
    Clin Pharmacol Ther 77:353-64. 2005
    The goal of this study was to define the haplotype structure of the cytochrome P450 (CYP) 2C9 gene in a European American population and evaluate associations between CYP2C9 haplotypes and anticoagulation-related outcomes.
  70. ncbi Distribution of soluble epoxide hydrolase, cytochrome P450 2C8, 2C9 and 2J2 in human malignant neoplasms
    Ahmed E Enayetallah
    Department of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, Storrs, CT 06269, USA
    J Mol Histol 37:133-41. 2006
    ..Our study warrants further investigation of the role of altered expression of these enzymes in neoplastic tissues...
  71. ncbi A warfarin-dosing model in Asians that uses single-nucleotide polymorphisms in vitamin K epoxide reductase complex and cytochrome P450 2C9
    Lai San Tham
    Department of Haematology Oncology, National University Hospital, and Translational Interface, Oncology Research Institute, Singapore
    Clin Pharmacol Ther 80:346-55. 2006
    ..in the Asian population, we hypothesize that single-nucleotide polymorphisms in cytochrome P450 (CYP) 2C9 (CYP2C9*3) and vitamin K epoxide reductase complex subunit 1 (VKORC1) at position 381, used to infer VKORC1haplotype in ..
  72. ncbi Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans
    S E Kimmel
    Department of Medicine, School of Medicine, University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, USA
    Pharmacogenomics J 8:53-60. 2008
    ..The association of APOE with warfarin dosing was independent of CYP2C9 and VKORC1 polymorphisms...
  73. ncbi The association of CYP2C9 gene polymorphisms with colorectal carcinoma in Han Chinese
    Ling Hong Liao
    Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, PR China
    Clin Chim Acta 380:191-6. 2007
    Cytochrome P450 (CYP) 2C9 is an important enzyme involved in xenobiotics metabolism. This study investigated the association of CYP2C9 gene coding region polymorphisms with colorectal cancer (CRC) in Chinese Han population.
  74. ncbi Warfarin metabolism and anticoagulant effect: a prospective, observational study of the impact of CYP2C9 genetic polymorphism in the presence of drug-disease and drug-drug interactions
    Mordechai Muszkat
    Division o f Medicine, Hadassah University Hospital, Jerusalem, Israel
    Clin Ther 29:427-37. 2007
    ..However, it is not known whether the CYP2C9 genotype contributes to the variability in warfarin dosage in the presence of drug-disease and drug-drug ..
  75. ncbi Combinations of cytochrome P450 gene polymorphisms enhancing the risk for sporadic colorectal cancer related to red meat consumption
    Sebastien Kury
    Laboratoire d Etude de l ADN, Faculté de Médecine de Nantes, 1 rue Gaston Veil, 44035 Nantes Cedex, France
    Cancer Epidemiol Biomarkers Prev 16:1460-7. 2007
    ..1548T>C in CYP1A2, g.-1293G>C and g.-1053C>T in CYP2E1, c.1294C>G in CYP1B1, and c.430C>T in CYP2C9)...
  76. ncbi Genetic polymorphisms of drug-metabolizing enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 in the Greek population
    Kostas Arvanitidis
    Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
    Fundam Clin Pharmacol 21:419-26. 2007
    ..the prevalence of the most common allelic variants of the polymorphic cytochrome P450 (CYP) enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 and to predict the genotype frequency for each polymorphism in the Greek population...
  77. pmc Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin
    N A Limdi
    Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA
    Clin Pharmacol Ther 83:312-21. 2008
    The association of CYP2C9 and VKORC1 1173C/T genotype and risk of hemorrhage among African Americans and European Americans is presented...
  78. ncbi Current pharmacogenetic developments in oral anticoagulation therapy: the influence of variant VKORC1 and CYP2C9 alleles
    Johannes Oldenburg
    Institute for Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Sigmund Freud Str 25, D 53105 Bonn, Germany
    Thromb Haemost 98:570-8. 2007
    ..Besides the known CYP2C9 variants that affect coumarin metabolism, the haplotype VKORC1*2 representing a frequent SNP within the VKORC1 ..
  79. doi Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes
    M S Wen
    Department of Internal Medicine, Section of Cardiology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
    Clin Pharmacol Ther 84:83-9. 2008
    Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose...
  80. pmc Warfarin pharmacogenetics: CYP2C9 and VKORC1 genotypes predict different sensitivity and resistance frequencies in the Ashkenazi and Sephardi Jewish populations
    Stuart A Scott
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA
    Am J Hum Genet 82:495-500. 2008
    ..b>CYP2C9( *)2 (p.R144C), CYP2C9( *)3 (p.I359L), and the VKORC1 promoter (g...
  81. doi VKORC1 and CYP2C9 polymorphisms are associated with warfarin dose requirements in Turkish patients
    G Oner Ozgon
    University of Istanbul, Istanbul, Turkey
    Eur J Clin Pharmacol 64:889-94. 2008
    The objective of this study was to determine the quantitative influence of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP 2C9) polymorphisms on warfarin dose requirements in Turkish patients.
  82. doi Relationship between CYP2C8 genotypes and diclofenac 5-hydroxylation in healthy Spanish volunteers
    P Dorado
    CICAB Extremadura University Hospital and Medical School, SES, Badajoz, Spain
    Eur J Clin Pharmacol 64:967-70. 2008
    ..5-hydroxylation, while, in vitro, the 4'-hydroxylation and 3'-hydroxylation seem to be mediated mainly by CYP2C9. We have demonstrated the relevance of CYP2C9 genotypes for diclofenac 4'-hydroxylation in healthy volunteers, so ..
  83. pmc Laboratory and clinical outcomes of pharmacogenetic vs. clinical protocols for warfarin initiation in orthopedic patients
    P A Lenzini
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Thromb Haemost 6:1655-62. 2008
    ..Warfarin is commonly prescribed for prophylaxis and treatment of thromboembolism after orthopedic surgery. During warfarin initiation, out-of-range International Normalized Ratio (INR) values and adverse events are common...
  84. doi Effects of CYP2C9 and VKORC1 on INR variations and dose requirements during initial phase of anticoagulant therapy
    Marta Spreafico
    A Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan and Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Via Pace 9, 20122 Milan, Italy
    Pharmacogenomics 9:1237-50. 2008
    ..However, they have a narrow therapeutic range and show inter- and intra-individual variability in dose requirement, largely conditioned by both environmental and genetic factors...
  85. pmc VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans
    Nita A Limdi
    Department of Neurology, University of Alabama at Birmingham, 1719 6th Avenue South, CIRC 312, Birmingham AL 35294 0021, USA
    Pharmacogenomics 9:1445-58. 2008
    Although the influence of VKORC1 and CYP2C9 polymorphisms on warfarin response has been studied, variability in dose explained by CYP2C9 and VKORC1 is lower among African-Americans compared with European-Americans...
  86. doi VKORC1 and CYP2C9 allelic variants influence acenocoumarol dose requirements in Greek patients
    Christos N Markatos
    Attikon University General Hospital, 23 27 Makrigianni Street, 11742 Athens, Greece
    Pharmacogenomics 9:1631-8. 2008
    To identify the frequencies of the polymorphisms CYP2C9*2, CYP2C9*3 and VKORC1-1639 G>A in the Greek population and investigate whether these polymorphisms and patient demographics (age, sex and comedication) could explain the ..
  87. doi Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose: a prospective study in Chinese patients
    Sheng Wen Huang
    Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guiyang, Guizhou, China
    Pharmacogenet Genomics 19:226-34. 2009
    ..To develop a warfarin-dosing algorithm that could be combined with pharmacogenomic and demographic factors, and to evaluate its effectiveness in a randomized prospective controlled clinical trial...
  88. doi A genome-wide association study of acenocoumarol maintenance dosage
    Martina Teichert
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
    Hum Mol Genet 18:3758-68. 2009
    ..0 x 10(-123)). The lowest P-value on chromosome 10 was obtained by rs4086116 within cytochrome P450 2C9 (CYP2C9) (P = 3.3 x 10(-24))...
  89. pmc CYP2C9*8 is prevalent among African-Americans: implications for pharmacogenetic dosing
    Stuart A Scott
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA
    Pharmacogenomics 10:1243-55. 2009
    ..differ among racial groups, most pharmacogenetic algorithms for genotype-guided warfarin dosing only include two CYP2C9 alleles (*2 and *3) and a single VKORC1 allele (g.-1639G>A or g.1173C>T) commonly found among Caucasians...
  90. doi Presence of CYP2C9*3 allele increases risk for hypoglycemia in Type 2 diabetic patients treated with sulfonylureas
    Georgia Ragia
    Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece
    Pharmacogenomics 10:1781-7. 2009
    ..Impaired metabolism of sulfonylureas due to gene polymorphisms in the metabolic enzyme CYP2C9 might lead to hypoglycemia...
  91. doi Genetic determinants of warfarin dosing in the Han-Chinese population
    M T Michael Lee
    Institute of Biomedical Sciences, Academia Sinica, 128, Academia Road, Section 2, Nankang, Taipei, Taiwan
    Pharmacogenomics 10:1905-13. 2009
    Warfarin, a widely prescribed oral anticoagulant, is used for the prevention of thromboembolism. Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements...
  92. doi Genetic and clinical predictors of warfarin dose requirements in African Americans
    L H Cavallari
    Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, Illinois, USA
    Clin Pharmacol Ther 87:459-64. 2010
    ..whether, in African-American patients, additional vitamin K oxidoreductase complex subunit 1 (VKORC1), cytochrome P450 2C9 (CYP2C9), CYP4F2, or apolipoprotein E (APOE) polymorphisms contribute to variability in the warfarin ..
  93. doi Distribution of the major cytochrome P450 (CYP) 2C9 genetic variants in a Saudi population
    Rajaa A Mirghani
    King Saud Bin Abdulaziz University for Health Sciences, King Fahad Medical City, Riyadh, Saudi Arabia
    Basic Clin Pharmacol Toxicol 109:111-4. 2011
    ..The CYP2C9 is a genetically polymorphic enzyme...
  94. pmc Influence of CYP2C9 and VKORC1 on patient response to warfarin: a systematic review and meta-analysis
    Andrea L Jorgensen
    Department of Biostatistics, Shelley s Cottage, University of Liverpool, Liverpool, United Kingdom
    PLoS ONE 7:e44064. 2012
    ..Finding the correct dose is difficult due to large inter-individual variability. Two genes, CYP2C9 and VKORC1, have been associated with this variability, leading to genotype-guided dosing tables in warfarin ..
  95. ncbi A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24
    I C Gray
    Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, England
    Genomics 28:328-32. 1995
    ..The cluster spans approximately 500 kb on proximal 10q24 and comprises four genes arranged in the order CYP2C8-CYP2C9-CYP2C19-CYP2C18. The map also includes an adjacent gene, the serum retinol binding protein gene (RBP4)...
  96. ncbi Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications
    G P Aithal
    Department of Medicine, University of Newcastle upon Tyne Medical School, UK
    Lancet 353:717-9. 1999
    The cytochrome P450 CYP2C9 is responsible for the metabolism of S-warfarin. Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single aminoacid substitution in each case...
  97. ncbi Genetic modulation of oral anticoagulation with warfarin
    M Margaglione
    Unita di Aterosclerosi e Trombosi, IRCCS Casa Sollievo della Sofferenza, S Giovanni Rotondo, Italy
    Thromb Haemost 84:775-8. 2000
    Cytochrome P450 CYP2C9 gene variants have been associated with hyperresponsiveness to small doses of warfarin and a higher bleeding complication rate...
  98. ncbi Pharmacogenetics of acenocoumarol: cytochrome P450 CYP2C9 polymorphisms influence dose requirements and stability of anticoagulation
    Dolors Tassies
    Hemotherapy and Hemostasis Department, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, Barcelona, Spain
    Haematologica 87:1185-91. 2002
    Cytochrome P4502C9 (CYP2C9) is the main enzyme implicated in coumarinic metabolism...
  99. pmc Validation of a new fluorogenic real-time PCR assay for detection of CYP2C9 allelic variants and CYP2C9 allelic distribution in a German population
    Maria Burian
    Pharmazentrum Frankfurt, Institut fur Klinische Pharmakologie, Klinikum der J W Goethe Universitat, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
    Br J Clin Pharmacol 54:518-21. 2002
    The aim was to develop a fast detection method for the polymorphic alleles related to impaired CYP2C9-mediated metabolism.
  100. ncbi CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers
    Pedro Dorado
    Department of Pharmacology and Psychiatry, Faculty of Medicine, University of Extremadura, Av De Elvas s n, 06071 Badajoz, Spain
    Eur J Clin Pharmacol 59:221-5. 2003
    This study analyzed the frequency of CYP2C9 variant alleles and evaluated the impact of CYP2C9 genotype on diclofenac metabolism in a Spanish population.
  101. ncbi Frequency of cytochrome P450 2C9 allelic variants in the Chinese and French populations
    Jue Quin Yang
    Pharmacology Department, Saint Antoine University Hospital University Pierre et Marie Curie Assistance Publique Hôpitaux de Paris, Paris, France
    Fundam Clin Pharmacol 17:373-6. 2003
    b>Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of different drugs with low therapeutic index such as oral anticoagulants. CYP2C9*2 and CYP2C9*3 are two single nucleotide polymorphic allelic variants...

Research Grants68

  1. Pharmacogenetics of ADRs: Warfarin Toxicity
    ALLAN EDWARD RETTIE; Fiscal Year: 2010
    ..In the previous funding period the focus was primarily on genetic variation within the cytochrome P450 enzyme, CYP2C9, because it controls metabolic clearance of the more potent (S) enantiomer of the racemic drug...
  2. Nita A Limdi; Fiscal Year: 2016
    ..Although this training grant focused on evaluating the influence of a single gene;cytochrome P450 2C9 (CYP2C9) genotype on warfarin dose, frequency of International Normalized Ratio (INR) outside target range, ..
  3. Pharmacogenetic Optimization of Analgesic Prescribing in Sickle Cell Disease
    Cheedy Jaja; Fiscal Year: 2013
    ..The study is designed to test the central hypothesis that deficient cytochrome CYP2C9, CYP2C19 and CYP2D6 metabolic phenotypes and suboptimal analgesic prescribing are positively associated with ED ..
  4. Pharmacogenetics and Drug Interactions
    Richard C Brundage; Fiscal Year: 2012
    ..A major finding from the previous granting period was that CYP2C9 variants with reduced function (i.e...
  5. NOVEL HIGH THROUGHPUT PLATFORM FOR SCREENING CYTOCHROME P450 INDUCTION
    MARIA INES MORANO; Fiscal Year: 2013
    ..In addition, we will expand the spectrum of reporters to include P450 CYP2C9 and CYP2C19, which are not commercially available...
  6. Comprehensive studies of novel SNPs affecting warfarin dose in African Americans
    Minoli Perera; Fiscal Year: 2012
    ..Currently, algorithms using polymorphisms in the CYP2C9 and VKORC1 genes have been developed to predict the correct maintenance dose of warfarin in Caucasians and Asians...
  7. The implementation of a pharmacogenomics-based algorithm for warfarin dosing
    Minoli Perera; Fiscal Year: 2013
    ..Currently, algorithms using genetic variants in CYP2C9 and VKORC1 have been developed to predict maintenance dose of warfarin in Caucasians and Asians...
  8. Personalized medicine informatics for anticoagulation therapy
    Roland Valdes; Fiscal Year: 2012
    ..of warfarin therapy will result from intelligent application of knowledge derived from inherited characteristics (CYP2C9 and VKORC1) of individual patients, only when this knowledge is applied through a standardized interventional ..
  9. Cytochrome P450 Eicosanoids and Myocardial Injury
    GARRETT JOHN GROSS; Fiscal Year: 2012
    Several recent studies demonstrated that hypoxia induces the expression of CYP epoxygenases, particularly CYP2C9, and EET production in several cell types...
  10. Paul R Ortiz de Montellano; Fiscal Year: 2014
    ..the prediction and rationalization of cytochrome P450 substrate and inhibitor specificity, focusing initially on CYP2C9 The work proposed in this application rests on a number of technical advances...
  11. Ambra Pozzi; Fiscal Year: 2016
    ..activation, reduces endothelial cell function in vitro and tumor growth and vascularization in vivo;4) the human CYP2C9, the metabolic homologue of Cyp2c44, is upregulated in the vasculature of human NSCLC;and 5) two CYP2C9 variants, ..
  12. Cytochrome P450 Derived Eicosanoids and Inflammation
    Craig R Lee; Fiscal Year: 2013
    ..Arachidonic acid is oxidatively metabolized by cytochrome P450 (CYP) epoxygenases from the CYP2J and CYP2C subfamilies to epoxyeicosatrienoic acids (EETs) in hepatic and extra-hepatic tissue...
  13. Effects of Anthocyanins on Cytochrome P450 Enzymes and P-glycoprotein
    MICHAEL JOHN HANLEY; Fiscal Year: 2012
    ..In preliminary work, blueberry juice inhibited the in vitro activity of CYP3A and CYP2C9 at concentrations that could easily be achieved in the gastrointestinal tract after BBJ consumption...
  14. MARKUS ALEXANDER LILL; Fiscal Year: 2014
    ..The new computational methods will be applied to two CYP enzymes (CYP2C9, 3A4) important in drug metabolism...
  15. Pharmacogenetics of Warfarin in Puerto Rican Patients using a Physiogenomics Appr
    Jorge Duconge; Fiscal Year: 2013
    ..past years in different populations worldwide, there is a fundamental gap in understanding whether variations in CYP2C9 and VKORC1 genes account for the inter-individual variability in response to warfarin that is observed in Puerto ..
  16. PHARMACOGENETICS IN SURGICAL CRITICAL CARE
    Bradley Freeman; Fiscal Year: 2004
    ..Warfarin is metabolized by two distinct subfamilies of the cytochrome P450 complex: CYP2A6 and CYP2C9. Common polymorphisms of these enzymes result in impaired warfarin metabolism...
  17. Randomized Clinical Trial of Genotype Guided Dosing of Warfarin Therapy
    STEPHEN KIMEL; Fiscal Year: 2013
    ..information and the individual's genotype relative to two genes known to influence warfarin metabolism (CYP2C9 and VKORC1 genes);2) initiation of warfarin therapy based on an algorithm using only clinical information;and 3) a ..
  18. Cost Effectiveness of Anticoagulation Versus Genetic Testing of CYP2C9 & VKORC1 G
    Anna Teschemaker; Fiscal Year: 2009
    ..The use of genetic testing for the CYP2C9 and VKORC1 genes in order to guide warfarin dosing for patients with VTE holds significant promise potentially to ..
  19. Modeling Genotype and other Factors to Enhance the Safety of Warfarin Prescribing
    Michael Caldwell; Fiscal Year: 2007
    ..by clinical factors including gender, age, body surface area, diabetes status, heart valves, concomitant use of CYP2C9 inducers, and genetic factors including CYP2C9 and VKORC1 genotype...
  20. Development of a Personalized Medicine Interface for the Safe and Effective Treat
    KRISTEN REYNOLDS; Fiscal Year: 2007
    ..Patient genotypes at two loci, CYP2C9 and VKORC1, will be utilized, as variants of these genes are closely associated with the reduced effectiveness of ..
  21. Pharmacogenetics of sulfamethoxazole in HIV/AIDS patients
    Danxin Wang; Fiscal Year: 2009
    ..by N-acetyltransferases 1 and 2 (NAT1 and NAT2);metabolic oxidation to toxic hydroxylamine derivatives by CYP2C9 and other (extra-) hepatic enzymes;protection from reactive oxygen species (ROS) by the glutathione (GSH) ..
  22. Aspirin pharmacogenetics in the Aspirin/Folate Polyp Prevention Trial
    KAREN MAKAR; Fiscal Year: 2009
    ..ALOX5);2) prostaglandin transport: multidrug resistance protein 4 (MRP4);and 3) aspirin metabolism: CYP2C9 and UGT1A6...
  23. Kathleen E Malone; Fiscal Year: 2014
    ..of TAM to its key metabolites are CYP2D6, CYP3A4, CYP3A5, but other important phase I and II enzymes include CYP2C9, CYP2C19, CYP2B6, CYP1B1, UGT2B7, UGT2B15, UGT1A4, UGT1A8, and UGT1A10...
  24. Inflamation and the Risk of Endometrial Cancer
    Akila Viswanathan; Fiscal Year: 2010
    ..The role of genetic polymorphisms of the enzymes CYP2C9 and UGT1A6 in the metabolism of aspirin in relation to its effect will be studied...
  25. Ethnic Variations in Antidepressant Response
    RUSSELL POLAND; Fiscal Year: 2005
    ..affecting the function of the serotonin transporter will predict responses to CU', whereas polymorphism of CYP2C 19 will be associated with the side effect profiles and pharmacokinetics of CIT...
  26. Role of CYP P450s in the Regulation of Vascular Tone through Adenosine Receptors
    S Jamal Mustafa; Fiscal Year: 2013
    ..whether the presence of A2A or A1 AR can have an effect on the VT through: (a) endothelium by preserving the CYP2C activity to generate EETs (EDHF);(b) smooth muscle CYP4A activity to form 20-HETE;(c) PKC and MAPK (ERK1/ERK2) ..
  27. Nancy J Brown; Fiscal Year: 2015
    ..b>Cyp2c and Cyp4a knockout mice will be used to study gene-dependent changes in: a) renal EET and/or 20-HETE synthase ..
  28. Nicola Marchi; Fiscal Year: 2016
    ..cells (EC) isolated from drug resistant epileptic patients (DRE);these include AED- metabolizers such as CYP3A4, CYP2C9, etc...
  29. Web-based Phenotyping for Genome Wide Association Studies of Drug Response
    Joanna L Mountain; Fiscal Year: 2010
    ..inhibitors (PPIs) and the gene CYP2C19, and between responses to several commonly used medications and the gene CYP2C9. The specific aims of this study are (1) to develop and administer web-based surveys to collect information ..
  30. Drug Metabolism and Chronic Liver Disease
    Robert Branch; Fiscal Year: 2005
    ..Part 1: A cocktail to include: caffeine (CYP1A2), flurbiprofen (CYP2C9), mephenytoin (CYP2C19), debrisoquine (CYP2D6), chlorzoxazone (CYP2E1) and dapsone (acetylation)...
  31. P450 Protein-Protein Interactions Determined by Selective Protein Manipulation
    TIMOTHY S contact TRACY; Fiscal Year: 2010
    ..Our central hypothesis is that CYP2C9-mediated metabolism kinetics measured in vitro are critically dependent on the state of oligomerization, and to ..
  32. BRIAN SCOTT DECKER; Fiscal Year: 2014
    ..Aim 2, blood samples will be drawn from subjects receiving thrice-weekly HD and incubated with human, recombinant CYP2C9, 2D6 and 3A4 hepatic microsomes. This experiment will then be repeated after the subjects are receiving SDHD...
  33. Effects of Ginseng and Ginkgo on Drug Disposition in Man
    Aryeh Hurwitz; Fiscal Year: 2003
    ..Losartan will be given separately for CYP2C9. These enzymes metabolize over 95 percent of clinically used drugs...
  34. STUDIES ON THE HALOGENATED AROMATIC HYDROCARBONS
    ALAN POLAND; Fiscal Year: 1990
    ..The induction of the microsomal monooxygenase, aryl hydrocarbon hydroxylase (AHH) activity, and other coordinately expressed enzymes, and the ..
  35. St. John's Wort and CYP3A Metabolism in Men & Women
    Reginald Frye; Fiscal Year: 2003
    ..John's Wort on other CYP pathways, specifically CYP1A2 using caffeine as a probe, CYP2C9 using flurbiprofen as a probe, and CYP2C19 using mephenytoin as a "cocktail" probe approach on the day following ..
  36. Modification of tamoxifen effectiveness by gene polymorphisms and other drugs
    Timothy Lash; Fiscal Year: 2009
    ..cancer recurrence in women (1) with genetic polymorphisms that reduce the enzyme function of CYP2D6, CYP3A5, or CYP2C9 to the rates of breast cancer recurrence in women who do not have these polymorphisms, (2) with genetic ..
  37. CHEMOPREVENTIVE AGENTS AND HUMAN CYTOCHROME P450 IN VIVO
    GRANT WILKINSON; Fiscal Year: 2002
    ..The CYP isoforms of interest and the associated in vivo probes will be CYP1A2 (caffeine), CYP2A6 (coumarin), CYP2C9 (tolbutamide), CYP2C19 (mephenytoin), CYP2D6 (debrisoquine), CYP2E1(chlorzoxazone) and CYP3A(midazolam)...
  38. RISK FACTORS FOR PHENYTOIN TOXICITY
    Sean Hennessy; Fiscal Year: 2005
    ..factors, including age and polymorphisms in the genes that express cytochrome P450 enzyme isoforms CYP2C19 and CYP2C9, which are responsible for phenytoin metabolism...
  39. HUMAN LIVER CYTOCHROMES P450
    Judy Raucy; Fiscal Year: 2002
    ..funding period noted that the antibiotic, rifampicin (RIF) induces proteins and mRNAs corresponding to CYP2C8, CYP2C9, and CYP2C19 in isolated human hepatocytes...
  40. Pharmacogenetics of Diabetes Prevention
    Richard Watanabe; Fiscal Year: 2009
    ..to be associated with response to troglitazone and to screen candidate genes;three cytochrome P-450 genes (CYP2C8, CYP2C9, and CYP3A4), which are involved in PIO metabolism;retinoid X receptor-a (RXRA) a critical co-factor for PPARG;and ..
  41. NSAIDS and Other Medications in Prostate Cancer Etiology
    Janet Stanford; Fiscal Year: 2005
    ..We also will assess genetic polymorphism in the CYP2C9 gene, which is involved in drug metabolism...
  42. Ethnic Variations in Antidepressant Response
    Ira Lesser; Fiscal Year: 2005
    ..g., CYP2C 19 and CYP3A4) that are responsible for the biotransformation of most antidepressants...
  43. Drug Metabolism, DNA Repair & Second Cancers
    Debra Friedman; Fiscal Year: 2003
    ..reductase (MTHFR), Glutathione-S-transferase (GST), GSTT1, GSTM1, GSTM3, GSTP1, Cytochrome P-450 (CYP) CYP2C9, CYP2C19, CYP3A4, thiopurine methyltransferase, methylguanine DNA methyltransferase, ERCC1, XPD, XRCC1, XRCC2, ..
  44. Pharmacogenetic Optimization of Anticoagulation Therapy
    Nita Limdi; Fiscal Year: 2007
    ..Warfarin is metabolized by Cytochrome P4502C9 (CYP2C9). There are several CYP2C9 alleles, which encode for enzymes with different catalytic activity...
  45. Medications, Genetic Variability & Breast Cancer
    Polly Newcomb; Fiscal Year: 2007
    ..Participants will contribute buccal cells for DNA to be genotyped for CYP2C9, UGTIA6, and CYP2D6 polymorphisms. We will also bank DNA for future gene-environment studies...
  46. SUPPRESSION OF P450 GENES BY INFLAMMATORY MEDIATORS
    Edward Morgan; Fiscal Year: 2004
    ..We will also characterize the regulation of human CYP2C genes in cultured human hepatocytes...
  47. DETERMINANTS OF INDIVIDUAL RESPONSIVENESS TO DRUGS
    CHARLES STEIN; Fiscal Year: 2006
    ..The feasibility of using a potent and specific MDR1 inhibitor to increase tissue and systemic drug bioavailability will be specifically addressed...
  48. HUMAN FMO'S DETERMINANTS OF SUBSTRATE SPECIFICITY
    Allan Rettie; Fiscal Year: 2004
    ..D) Determine the mechanism underlying loss of function in FMO3 variants associated with trimethylaminuria as a further test of the model. (E) Prepare diffraction quality crystals of CMO. ..
  49. Pharmacogenetics and Antithrombotic Therapy
    Brian Gage; Fiscal Year: 2003
    ..We propose to complete our genotyping of these specimens for single nucieotide polymorphisms (SNPs) of the cytochrome P450 2C9 gene...
  50. Active Site Models of CYP4 Enzymes
    ALLAN EDWARD RETTIE; Fiscal Year: 2010
    ..abstract_text> ..
  51. BETA-ADRENERGIC RECEPTOR POLYMORPHISMS AND HYPERTENSION
    Julie Johnson; Fiscal Year: 2003
    ..the BAR genotype significantly impacts the BP response to B-blockers could lead to improved patient outcomes, as patients could be genotyped prior to institution of B-blocker therapy, thus avoiding this therapy in those likely to respond ..
  52. Hypertension Pharmacogenetics
    Julie Johnson; Fiscal Year: 2006
    ..The proposed studies should add substantial new information about antihypertensive pharmacogenetics, and could influence how antihypertensive medications are prescribed in the future. ..
  53. NADPH-DEPENDENT METABOLISM OF ARACHIDONIC ACID
    Jorge Capdevila; Fiscal Year: 2008
    ..identified as mediators of vascular reactivity, ion transport, and transmembrane signaling, and alterations in CYP2C and 4A function associated with the pathophysiology of cardiovascular disease...
  54. Beta-receptors and cardiovascular pharmacogenomics
    Julie Johnson; Fiscal Year: 2006
    ..abstract_text> ..
  55. Beta-adrenoceptor genetic polymorphisms and obesity
    Julie Johnson; Fiscal Year: 2002
    ..Additionally, genotyping individuals early in age may help to identify those at increased risk of obesity prior to them becoming obese so that they may take appropriate preventive measures. ..
  56. CYP2J2 Derived Eicosanoids and Endothelial Function
    Craig Lee; Fiscal Year: 2005
    ..abstract_text> ..
  57. Metabolism and Pharmacogenetics in MDMA-Induced Toxicity
    Rafael de la Torre; Fiscal Year: 2009
    ..A study will compare MDMA toxicity when co-adminsitered with the MRP1 inhibitor probenecid. ..
  58. MALDI-TOF MS for High Throughput SNP Analysis
    ALAN SHULDINER; Fiscal Year: 2002
    ..The technology will be of great benefit to a large number of NIH-funded projects and researchers, opportunities and will greatly accelerate the pace of discovery in this post-genomic era. ..
  59. Mechanisms of Vanilloid Receptor-Induced Cell Death
    Christopher Reilly; Fiscal Year: 2005
    ..Outcomes of these investigations can be utilized to predict human responses to respiratory irritants in self-defense weaponry and define the functions of vanilloid receptors lung epithelial cells. ..
  60. ADVANCES IN SELENIUM SUPPLEMENTATION
    Michael Franklin; Fiscal Year: 2006
    ..abstract_text> ..
  61. Role of EETs in Growth of Human Endothelial Cells
    Meetha Medhora; Fiscal Year: 2006
    ..It will impact on the potential for development of EETs as therapeutic agents during and after cardiac ischemia and acute lung injury. ..
  62. HMGB1/2 and Cellular Response to Fraudulent Nucleosides
    Evgeny Krynetskiy; Fiscal Year: 2007
    ..abstract_text> ..
  63. OLFACTORY TOXICITY OF ENVIRONMENTAL AGENTS
    Xinxin Ding; Fiscal Year: 2010
    ....
  64. Mechanisms of Atypical Drug Kinetics and Interactions
    TIMOTHY TRACY; Fiscal Year: 2008
    ..Increases in P450 reaction efficiency and reductions in reaction cycle uncoupling also have been observed during CYP2C9 heteroactivation, but preliminary data suggest that not all activator compounds act by the same mechanism...
  65. Isothiocyanates as specific antagonists of human SXR
    David Eaton; Fiscal Year: 2009
    ..Finally, they could help to further elucidate the risks and benefits of sulforaphane, a potential dietary phytochemical that has been proposed as a safe 'nutraceutical'compound to reduce cancer risk. ..
  66. MECHANISMS OF TOXICITY GORDON CONFERENCE
    RONALD HINES; Fiscal Year: 2002
    ..There also is substantial involvement of new personnel as Chairs and co-Chairs. Thus, the Mechanism of Toxicity GRC is poised to continue its growth as the single leading small conference on Molecular Toxicology. ..
  67. Microdevice for Direct DNA Purification
    James Landers; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  68. SIGNIFICANCE OF GENETIC VARIATION IN ESTROGEN METABOLISM
    David Eaton; Fiscal Year: 2001
    ..abstract_text> ..