aryl hydrocarbon hydroxylases

Summary

Summary: A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.

Top Publications

  1. ncbi Metabolism and disposition kinetics of nicotine
    Janne Hukkanen
    Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco Genreral Hospital Medical Center, and the Department of Medicine, University of California, San Francisco, Box 1220, San Francisco, CA 94143 1220, USA
    Pharmacol Rev 57:79-115. 2005
  2. pmc Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis
    Jessica L Mega
    TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    JAMA 304:1821-30. 2010
  3. ncbi CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and meta-analysis
    Michael V Holmes
    Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, 1 19 Torrington Pl, London, WC1E 6BT, United Kingdom
    JAMA 306:2704-14. 2011
  4. pmc Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing
    J A Johnson
    Department of Pharmacotherapy and Translational Research, College of Pharmacy, and Center for Pharmacogenomics, University of Florida, Gainesville, Florida, USA
    Clin Pharmacol Ther 90:625-9. 2011
  5. ncbi Cytochrome p-450 polymorphisms and response to clopidogrel
    Jessica L Mega
    Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    N Engl J Med 360:354-62. 2009
  6. ncbi Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation
    Jeffrey L Anderson
    Cardiovascular Department, LDS Hospital, Intermountain Healthcare, Salt Lake City, UT, USA
    Circulation 116:2563-70. 2007
  7. pmc Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin
    B F Gage
    Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA
    Clin Pharmacol Ther 84:326-31. 2008
  8. ncbi Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial
    Jason D Roberts
    Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada
    Lancet 379:1705-11. 2012
  9. 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
  10. ncbi Pharmacogenetics: from bench to byte--an update of guidelines
    J J Swen
    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
    Clin Pharmacol Ther 89:662-73. 2011

Research Grants

  1. CIGARETTE SMOKING OR PCBS EFFECTS ON ESTRADIOL
    Bao Ting Zhu; Fiscal Year: 1999
  2. Insecticide Resistance:CYP6D1 Regulation and Alleles
    Jeffrey Scott; Fiscal Year: 2005
  3. Pharmacogenetic Optimization of Anticoagulation Therapy
    Nita Limdi; Fiscal Year: 2007
  4. Novel noninvasive assessment of cytochrome P450 activity
    Evan Kharasch; Fiscal Year: 2009
  5. ANESTHETIC RENAL METABOLISM--MECHANISMS AND CONSEQUENCES
    Evan Kharasch; Fiscal Year: 2002
  6. MDR1 and Related Proteins during HIV PI Exposure
    David Greenblatt; Fiscal Year: 2005
  7. HAART Regimens in Substance Abusers
    David Greenblatt; Fiscal Year: 2003
  8. CHRONIC BENZODIAZEPINES: BEHAVIOR AND NEUROCHEMISTRY
    David Greenblatt; Fiscal Year: 2005
  9. GARLIC PREPARATIONS AND ANTIRETROVIRAL DRUGS
    David Greenblatt; Fiscal Year: 2004
  10. Metabolic Consequences of HAART: CYP3A and P-gp
    David Greenblatt; Fiscal Year: 2003

Detail Information

Publications298 found, 100 shown here

  1. ncbi Metabolism and disposition kinetics of nicotine
    Janne Hukkanen
    Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco Genreral Hospital Medical Center, and the Department of Medicine, University of California, San Francisco, Box 1220, San Francisco, CA 94143 1220, USA
    Pharmacol Rev 57:79-115. 2005
    ..Due to the significance of the CYP2A6 enzyme in nicotine clearance, special emphasis is given to the effects and population distributions of CYP2A6 alleles and the regulation of CYP2A6 enzyme...
  2. pmc Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis
    Jessica L Mega
    TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    JAMA 304:1821-30. 2010
    ..Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes...
  3. ncbi CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and meta-analysis
    Michael V Holmes
    Genetic Epidemiology Group, Department of Epidemiology and Public Health, University College London, 1 19 Torrington Pl, London, WC1E 6BT, United Kingdom
    JAMA 306:2704-14. 2011
    ....
  4. pmc Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing
    J A Johnson
    Department of Pharmacotherapy and Translational Research, College of Pharmacy, and Center for Pharmacogenomics, University of Florida, Gainesville, Florida, USA
    Clin Pharmacol Ther 90:625-9. 2011
    ..pharmgkb.org based on new developments in the field.(1)...
  5. ncbi Cytochrome p-450 polymorphisms and response to clopidogrel
    Jessica L Mega
    Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    N Engl J Med 360:354-62. 2009
    ..Clopidogrel requires transformation into an active metabolite by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. The genes encoding CYP enzymes are polymorphic, with common alleles conferring reduced function...
  6. ncbi Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation
    Jeffrey L Anderson
    Cardiovascular Department, LDS Hospital, Intermountain Healthcare, Salt Lake City, UT, USA
    Circulation 116:2563-70. 2007
    ..Pharmacogenetic-guided dosing of warfarin is a promising application of "personalized medicine" but has not been adequately tested in randomized trials...
  7. pmc Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin
    B F Gage
    Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA
    Clin Pharmacol Ther 84:326-31. 2008
    ..To facilitate use of these pharmacogenetic and clinical algorithms, we developed a nonprofit website, http://www.WarfarinDosing.org...
  8. ncbi Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial
    Jason D Roberts
    Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada
    Lancet 379:1705-11. 2012
    ..We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI...
  9. 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
    ..5% of dose variance. These GWAS results provide further impetus for conducting large-scale trials assessing patient benefit from genotype-based forecasting of warfarin dose...
  10. ncbi Pharmacogenetics: from bench to byte--an update of guidelines
    J J Swen
    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands
    Clin Pharmacol Ther 89:662-73. 2011
    ....
  11. pmc CYP2C19 variation and citalopram response
    David A Mrazek
    Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    Pharmacogenet Genomics 21:1-9. 2011
    ..Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role...
  12. ncbi Frequencies of poor metabolizers of cytochrome P450 2C19 in esophagus cancer, stomach cancer, lung cancer and bladder cancer in Chinese population
    Wei Xing Shi
    Department of Public Health, School of Medicine, Zhejiang University, Hangzhou 310031, Zhejiang Province, China
    World J Gastroenterol 10:1961-3. 2004
    ..To investigate the association between cytochrome P450 2C19 (CYP2C19) gene polymorphism and cancer susceptibility by genotyping of CYP2C19 poor metabolizers (PMs) in cancer patients...
  13. ncbi Effect of CYP2C19*17 gene variant on Helicobacter pylori eradication in peptic ulcer patients
    Mateusz Kurzawski
    Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp 72, 70 111, Szczecin, Poland
    Eur J Clin Pharmacol 62:877-80. 2006
    ..In the present study, a potential association between CYP2C19*17 allele and lower H. pylori eradication efficacy was tested in a group of peptic ulcer patients...
  14. ncbi A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants
    Sarah C Sim
    Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm
    Clin Pharmacol Ther 79:103-13. 2006
    ..A significant portion of extensive metabolizers do not reach appropriate drug levels, and our objective was to investigate any genetic background...
  15. ncbi Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects
    Jean Sebastien Hulot
    INSERM U 765, Service d Hématologie Biologique A, Hopital Europeen Georges Pompidou, 20 rue Leblanc, 75908 Paris Cedex 15, France
    Blood 108:2244-7. 2006
    ....
  16. ncbi Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver
    T Lang
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Pharmacogenetics 11:399-415. 2001
    ..These data demonstrate that the extensive interindividual variability of CYP2B6 expression and function is not only due to regulatory phenomena, but also caused by a common genetic polymorphism...
  17. 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
    ..Provided that they are validated, our results suggest the need to develop robust combinative methods to improve genetic investigations into the susceptibility to CRC...
  18. pmc Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism
    David Burger
    Radboud University Medical Center Nijmegen, The Netherlands
    Br J Clin Pharmacol 61:148-54. 2006
    ..To characterize the demographic and pharmacogenetic factors that influence interpatient variability in the plasma concentrations of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz...
  19. pmc Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk
    Sean P Cleary
    Cancer Care Ontario, Toronto, Ontario, Canada
    Am J Epidemiol 172:1000-14. 2010
    ..03) status. These findings support the hypothesis that prolonged cigarette smoking is associated with increased risk of colorectal cancer and that this risk may be modified by variation in carcinogen metabolism genes...
  20. 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
    ..Individualisation of dose is essential for those CYP2C9 substrates with a narrow therapeutic index...
  21. ncbi Association of poor metabolizers of cytochrome P450 2C19 with head and neck cancer and poor treatment response
    Sunishtha S Yadav
    Developmental Toxicology Division, Indian Institute of Toxicology Research formerly Industrial Toxicology Research Centre, CSIR P O Box 80, M G Marg, Lucknow 226001, India
    Mutat Res 644:31-7. 2008
    ....
  22. ncbi CYP2B6 polymorphisms influence the plasma concentration and clearance of the methadone S-enantiomer
    Sheng Chang Wang
    Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
    J Clin Psychopharmacol 31:463-9. 2011
    ..0001, respectively). We conclude that genetic polymorphisms in the CYP2B6 gene may therefore be indicators of the clearance, plasma concentration and C/D ratio of S-methadone...
  23. pmc Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis
    Tim Bauer
    Department of Pharmacology, University Hospital of Cologne, D 50931 Cologne, Germany
    BMJ 343:d4588. 2011
    ..To evaluate the accumulated information from genetic association studies investigating the impact of variants of the cytochrome P450 (CYP) 2C19 genotype on the clinical efficacy of clopidogrel...
  24. 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
    ..Based upon the data, a new warfarin dosing regimen has been developed. The validity of the dosing regimen was confirmed in a second cohort of patients on warfarin therapy...
  25. ncbi The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity
    Bryan A Ward
    Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    J Pharmacol Exp Ther 306:287-300. 2003
    ..Efavirenz may be a valuable phenotyping tool to study the role of CYP2B6 in human drug metabolism...
  26. pmc Clopidogrel: a case for indication-specific pharmacogenetics
    J A Johnson
    College of Pharmacy and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA
    Clin Pharmacol Ther 91:774-6. 2012
    ....
  27. ncbi Modification of ocular defects in mouse developmental glaucoma models by tyrosinase
    Richard T Libby
    Jackson Laboratory, Bar Harbor, ME 04609, USA
    Science 299:1578-81. 2003
    ..These experiments raise the possibility that a tyrosinase/l-dopa pathway modifies human PCG, which could open new therapeutic avenues...
  28. ncbi 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
    ..Besides age, gender, body mass index and target INR, one polymorphism within each of the VKORC1, CYP2C9, CYP4F2 and CYP2C18 genes could explain 48.8% of acenocoumarol dosage variation...
  29. ncbi Genetic determinants of response to clopidogrel and cardiovascular events
    Tabassome Simon
    Assistance Publique Hopitaux de Paris, Hopital Saint Antoine, and Universite Pierre et Marie Curie, Paris 06, France
    N Engl J Med 360:363-75. 2009
    ..The effect of these determinants on clinical outcomes after an acute myocardial infarction is unknown...
  30. ncbi Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response
    J Kirchheiner
    Institute of Clinical Pharmacology, Campus Charite Mitte, University Medicine Berlin, Berlin, Germany
    Mol Psychiatry 9:442-73. 2004
    ....
  31. 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
    ..The newly discovered binding pocket also suggests that CYP2C9 may simultaneously accommodate multiple ligands during its biological function, and provides a possible molecular basis for understanding complex drug-drug interactions...
  32. ncbi Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study
    Jean Philippe Collet
    Institut de Cardiologie, INSERM 856, Universite Paris 6, hôpital Pitié Salpêtrière AP HP, Paris, France
    Lancet 373:309-17. 2009
    ..We assessed whether the CYP2C19*2 polymorphism affected long-term prognosis of patients who were chronically treated with clopidogrel...
  33. ncbi Clinical significance of the cytochrome P450 2C19 genetic polymorphism
    Zeruesenay Desta
    Division of Clinical Pharmacology, Indiana University School of Medicine, Wishard Hospital, Indianapolis 46202, USA
    Clin Pharmacokinet 41:913-58. 2002
    ..Finally, many studies have attempted to identify relationships between CYP2C19 genotype and phenotype and susceptibility to xenobiotic-induced disease, but none of these are compelling...
  34. pmc Impact of CYP2D6, CYP3A5, CYP2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients
    Joanne S L Lim
    Laboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore
    Br J Clin Pharmacol 71:737-50. 2011
    ..To investigate the impact of genetic polymorphisms in CYP2D6, CYP3A5, CYP2C9 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Asian breast cancer patients...
  35. pmc Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups
    Stuart A Scott
    Department of Genetics and Genomic Sciences, Box 1498, Mount Sinai School of Medicine of New York University, Fifth Avenue at 100th Street, New York, NY 10029, USA
    Pharmacogenomics 11:781-91. 2010
    ..Thus, we determined the individual and combined frequencies of important CYP2C9, VKORC1 and CYP4F2 variants in several racial/ethnic groups...
  36. pmc Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers
    Stephanie R Faucette
    Division of Molecular Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA
    J Pharmacol Exp Ther 320:72-80. 2007
    ..Our results demonstrate that CMZ, EFV, and NVP induce CYP2B6 and CYP3A4 preferentially through hCAR and that hCAR3 represents a sensitive tool for in vitro prediction of chemical-mediated human CAR activation...
  37. ncbi No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting
    Dirk Sibbing
    Deutsches Herzzentrum München and 1 Medizinische Klinik, Klinikum rechts der Isar, Technische Universitat Munchen, Lazarettstrasse 36, Munich, Germany
    Eur Heart J 32:1605-13. 2011
    ..The aim of this study was to assess the impact of the PON1 Q192R genotype in parallel to that of CYP2C19*2 on the antiplatelet effect of clopidogrel and the risk of ST in clopidogrel-treated patients...
  38. pmc Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis
    Jessica L Mega
    TIMI Study Group, Cardiovascular Division, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Lancet 376:1312-9. 2010
    ..We also assessed the effect of genotype on the pharmacodynamic and pharmacokinetic properties of these drugs in healthy individuals...
  39. ncbi The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis
    Daniel W Nebert
    Department of Environmental Health, and Center for Environmental Genetics, University of Cincinnati Medical Center, P O Box 670056, Cincinnati, Ohio 45267 0056, USA
    Nat Rev Cancer 6:947-60. 2006
    ..We suggest a two-tiered system to predict an overall inter-individual risk of tumorigenesis based on DNA variants in certain 'early defence' CYP genes, combined with polymorphisms in various downstream target genes...
  40. ncbi Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients
    E Ngaimisi
    Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden
    Clin Pharmacol Ther 88:676-84. 2010
    ..The cumulative induction may influence the long-term antiretroviral therapy outcome, particularly in CYP2B6*1 carriers...
  41. ncbi Epoxide hydrolase and CYP2C9 polymorphisms, cigarette smoking, and risk of colorectal carcinoma in the Nurses' Health Study and the Physicians' Health Study
    Gregory J Tranah
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
    Mol Carcinog 44:21-30. 2005
    ..Our results indicate that individuals exposed to tobacco carcinogens were at increased risk of colorectal cancer and that overall risk is related to mEH and CYP2C9 genotype, although the results were not consistent between men and women...
  42. ncbi Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine?
    Jose A G Agundez
    Department of Pharmacology, University of Extremadura, Medical School, Badajoz, Spain
    Expert Opin Drug Metab Toxicol 5:607-20. 2009
    ....
  43. 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
    ..The differences in allele frequencies of A/G allele and its levels of VKORC1 promoter activity may underscore the inter-individual differences in warfarin dosage as well as inter-ethnic differences between Chinese and Caucasians...
  44. ncbi High doses of clopidogrel to overcome genetic resistance: the randomized crossover CLOVIS-2 (Clopidogrel and Response Variability Investigation Study 2)
    Jean Philippe Collet
    Institut de Cardiologie, INSERM CMR937, Hôpital Pitié Salpêtrière Assistance Publique Hôpitaux de Paris, Université Pierre et Marie Curie UPMC, Paris VI, Paris, France
    JACC Cardiovasc Interv 4:392-402. 2011
    ..This study sought to determine whether the pharmacokinetic (PK) and pharmacodynamic (PD) responses to high or standard clopidogrel loading doses (LDs) differ according to CYP2C19*2 allele...
  45. 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
    ..The aims of this study were to derive a pharmacogenetics-based dosing algorithm by use of retrospective information and to validate it through a data-splitting method in a separate cohort of equal size...
  46. ncbi Tribal ethnicity and CYP2B6 genetics in Ugandan and Zimbabwean populations in the UK: implications for efavirenz dosing in HIV infection
    Y Jamshidi
    Division of Biomedical Sciences, St George s, University of London, London, UK
    J Antimicrob Chemother 65:2614-9. 2010
    ..To determine differences in CYP2B6 loss of function (LoF) single nucleotide polymorphisms (SNPs) and haplotypes between Zimbabweans and Ugandans, and within Ugandan populations (Bantu and Nilotic)...
  47. ncbi Induction of cytochrome P450 2B6 activity by the herbal medicine baicalin as measured by bupropion hydroxylation
    Lan Fan
    Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, People s Republic of China
    Eur J Clin Pharmacol 65:403-9. 2009
    ..This study investigated the effect of the herbal medicine baicalin on bupropion hydroxylation, a probe reaction for CYP2B6 activity related to different CYP2B6 genotype groups...
  48. pmc Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study
    Jackson K Mukonzo
    Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, SE 141 86, Stockholm, Sweden
    BMC Infect Dis 13:261. 2013
    ..We evaluated the influence of rifampicin cotreatment, efavirenz pharmacokinetics and pharmacogenetics on neuropsychiatric disorders in Ugandan HIV patients with or without tuberculosis coinfection...
  49. ncbi Functional characterization of CYP2B6 allelic variants in demethylation of antimalarial artemether
    Masashi Honda
    Laboratory of Pharmacotherapy of Life Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan
    Drug Metab Dispos 39:1860-5. 2011
    ..14, CYP2B6.20 and CYP2B6.27) exhibited significantly lower V(max) compared with that of CYP2B6.1. This functional analysis of CYP2B6 variants could provide useful information for individualization of antimalarial drug therapy...
  50. ncbi Polymorphisms associated with circulating sex hormone levels in postmenopausal women
    Alison M Dunning
    Cancer Research UK, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK
    J Natl Cancer Inst 96:936-45. 2004
    ..We investigated the association between levels of sex hormones and single nucleotide polymorphisms (SNPs) in genes coding for the enzymes that regulate them...
  51. ncbi Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen
    Masatsugu Okishiro
    Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
    Cancer 115:952-61. 2009
    ....
  52. ncbi Cytochrome P450 1B1: a novel anticancer therapeutic target
    Morag C E McFadyen
    Robert Gordon University, School of Pharmacy, Schoolhill, Aberdeen, AB10 1FR, UK
    Future Oncol 1:259-63. 2005
    ..The therapeutic strategy, which is at the most advanced stage of development, is a CYP1B1-based vaccine which has already successfully completed a Phase I clinical trial...
  53. ncbi Common polymorphisms in CYP2C9, subclinical atherosclerosis and risk of ischemic vascular disease in 52,000 individuals
    D Kaur-Knudsen
    Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, DK 2730 Herlev, Denmark
    Pharmacogenomics J 9:327-32. 2009
    ....
  54. ncbi Cytochrome P450 interactions in human cancers: new aspects considering CYP1B1
    Peter H Roos
    Institut fur Arbeitsphysiologie an der Universitat Dortmund IfADo, Leibniz Research Centre for Working Environment and Human Factors, Ardeystr 67, D 44139 Dortmund, Germany
    Expert Opin Drug Metab Toxicol 1:187-202. 2005
    ..It appears that CYP1B1 plays a key role for the activation of carcinogens at several organ targets, with a likelihood of complex gene-environment interactions implying Phase II enzymes...
  55. pmc Antiproliferative and cytostatic effects of the natural product eupatorin on MDA-MB-468 human breast cancer cells due to CYP1-mediated metabolism
    Vasilis Androutsopoulos
    Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, UK
    Breast Cancer Res 10:R39. 2008
    ..In this study, we aimed to identify a possible mechanism of action for the antiproliferative effect of eupatorin, which can be attributed to CYP1 family-mediated metabolism...
  56. ncbi Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz
    Kathrin Klein
    Dr Margarete Fischer Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
    Pharmacogenet Genomics 15:861-73. 2005
    ..17 (T26S, D28G, R29T) appeared to be functionally normal. These data extend the CYP2B6 knowledge base and should be particularly relevant for anti-HIV-therapy with efavirenz...
  57. pmc New genetic variant that might improve warfarin dose prediction in African Americans
    Hedi Schelleman
    Center for Clinical Epidemiology and Biostatistics, Department of Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Pittsburgh, PA 19104 6021, USA
    Br J Clin Pharmacol 70:393-9. 2010
    ..However, these factors seem to explain less of the dose variability in African Americans who have a lower prevalence of the CYP2C9*2 and *3 and VKORC1 1173T alleles...
  58. ncbi CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients
    Jean Sebastien Hulot
    Universite Pierre et Marie Curie Paris 6, INSERM UMR S 956, Pharmacology Department, Pitie Salpetriere University Hospital, Paris, France
    Circ Cardiovasc Interv 4:422-8. 2011
    ..We tested the effects of PON1 polymorphisms on clopidogrel pharmacokinetics and pharmacodynamics and the occurrence of cardiovascular outcomes in young post-myocardial infarction (MI) patients treated with clopidogrel...
  59. pmc Maternal dioxin exposure combined with a diet high in fat increases mammary cancer incidence in mice
    Michele La Merrill
    Department of Genetics, Center for Environmental and Health Susceptibility, Lineberger Cancer Center, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA
    Environ Health Perspect 118:596-601. 2010
    ....
  60. ncbi Long-term effect of efavirenz autoinduction on plasma/peripheral blood mononuclear cell drug exposure and CD4 count is influenced by UGT2B7 and CYP2B6 genotypes among HIV patients
    Abiy Habtewold
    Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1 68, Karolinska Institutet, Stockholm, Sweden
    J Antimicrob Chemother 66:2350-61. 2011
    ..We investigated the long-term effect of efavirenz autoinduction on its plasma/peripheral blood mononuclear cell (PBMC) exposure and the CD4 count, and the importance of sex and pharmacogenetic variations...
  61. ncbi Screening glaucoma genes in adult glaucoma suggests a multiallelic contribution of CYP1B1 to open-angle glaucoma phenotypes
    Hussain Y Patel
    Department of Ophthalmology, Faculty of Medical and Health Sciences, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand
    Clin Experiment Ophthalmol 40:e208-17. 2012
    ..We aimed to determine the mutational spectrum and frequency in the genes implicated in glaucoma, in a range of glaucoma and 'glaucoma suspect' (GS) participants, with a positive family history...
  62. ncbi Optimization of warfarin dose by population-specific pharmacogenomic algorithm
    A Pavani
    Department of Clinical Pharmacology and Therapeutics, Nizam s Institute of Medical Sciences, Hyderabad, India
    Pharmacogenomics J 12:306-11. 2012
    ..06 vs 0.50) and underestimation (0.13 vs 0.48). To conclude, this population-specific algorithm has greater clinical utility in optimizing the warfarin dose, thereby decreasing the adverse effects of suboptimal dose...
  63. ncbi CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans
    Milimo Maimbo
    Laboratory for International Alliance, RIKEN Center for Genomic Medicine, 1 7 22 Suehiro cho, Tsurumi ku, Yokohama, 230 0045, Japan
    Eur J Clin Pharmacol 68:267-71. 2012
    ..In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in these genes with plasma efavirenz levels in Zimbabwean human immunodeficiency virus (HIV)-positive patients treated with efavirenz...
  64. pmc The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors
    Steven Lane
    Department of Biostatstics, Brownlow Street, University of Liverpool, Liverpool L69 3GS, UK
    Br J Clin Pharmacol 73:66-76. 2012
    ..The interindividual variability in dose requirements is influenced by a number of factors, including polymorphisms in genes mediating warfarin pharmacology, co-medication, age, sex, body size and diet...
  65. ncbi Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data
    Craig R Lee
    Division of Pharmacotherapy, University of North Carolina at Chapel Hill, 27599 7360, USA
    Pharmacogenetics 12:251-63. 2002
    ..However, further clinical investigations evaluating the metabolic consequences in individuals expressing the CYP2C9*2, *3, *4, *5, or *6 alleles are required before large-scale clinical genotyping can be recommended...
  66. pmc Decreased warfarin clearance associated with the CYP2C9 R150H (*8) polymorphism
    Y Liu
    Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA
    Clin Pharmacol Ther 91:660-5. 2012
    ..This finding provides clinical and experimental evidence to explain the lower warfarin dose requirements in patients with the CYP2C9*8 allele...
  67. ncbi Design, synthesis and evaluation of the inhibitory selectivity of novel trans-resveratrol analogues on human recombinant CYP1A1, CYP1A2 and CYP1B1
    Renata Mikstacka
    Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Grunwaldzka 6, 60 780 Poznan, Poland
    Bioorg Med Chem 20:5117-26. 2012
    ..Structure-activity relationship analysis rendered better understanding of the mechanism of action of xenobiotic-metabolizing enzymes crucial at the early stage of carcinogenesis...
  68. pmc Reproducibility of the nicotine metabolite ratio in cigarette smokers
    Gideon St Helen
    Center for Tobacco Control Research and Education, University of California, San Francisco, San Francisco, CA 94143, USA
    Cancer Epidemiol Biomarkers Prev 21:1105-14. 2012
    ....
  69. ncbi CYP2C9 and CYP2C19 genetic polymorphisms: frequencies in the south Indian population
    Rosemary Jose
    Pharmacogenomics Laboratory, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER, Pondicherry, India
    Fundam Clin Pharmacol 19:101-5. 2005
    ..CYP2C19*2 was higher than in other major populations reported so far. The relatively high CYP2C19 poor-metabolizer genotype frequency of 12.6% indicates that over 28 million south Indians are poor metabolizers of CYP2C19 substrates...
  70. ncbi Frequencies of VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 genetic variants in the Northern Indian population
    Saurabh S Rathore
    Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
    Biosci Trends 4:333-7. 2010
    ..VKORC1 -1639 G>A allele is present at moderately high frequency in the Northern Indian population. The frequencies of CYP2C9*2 and CYP2C9*3 alleles are also found to be different from other populations...
  71. ncbi The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis
    Sara Padol
    Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada
    Am J Gastroenterol 101:1467-75. 2006
    ..We conducted a meta-analysis to investigate the evidence relating CYP2C19 to first-line H. pylori eradication rates...
  72. ncbi Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin
    David A Flockhart
    Indiana University School of Medicine, Indianapolis, Indiana, USA
    Genet Med 10:139-50. 2008
    ....
  73. 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
    ....
  74. pmc Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes
    Alison E Aitken
    Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Drug Metab Dispos 35:1687-93. 2007
    ..Our results show that human CYP2C8, 2C9, 2C18, 2C19, 2B6, and 3A4 responses to inflammation are independently regulated and indicate that this fine control may have a critical effect on human drug responses in disease states...
  75. 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...
  76. ncbi Effects of CYP2C19, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxicillin, and metronidazole
    Barbara Gawronska-Szklarz
    Department of Pharmacology, Pomeranian Medical University, Powstancow Wlkp 72, 70 111, Szczecin, Poland
    Eur J Clin Pharmacol 66:681-7. 2010
    ..pylori in Polish Caucasian patients treated with a triple therapy of pantoprazole, amoxicillin, and metronidazole...
  77. ncbi Lung tumorigenesis promoted by anti-apoptotic effects of cotinine, a nicotine metabolite through activation of PI3K/Akt pathway
    Tomohisa Nakada
    Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    J Toxicol Sci 37:555-63. 2012
    ..We herein propose that cotinine induces tumor promotion by inhibiting apoptosis and enhancing cellular proliferation, thus underlining the importance of CYP2A6 in tobacco-related lung tumorigenesis...
  78. ncbi A prospective study of genetic polymorphisms in the cytochrome P-450 2C9 enzyme and the risk for distal colorectal adenoma
    Andrew T Chan
    Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA
    Clin Gastroenterol Hepatol 2:704-12. 2004
    ..Genetic variation in this enzyme may modulate the influence of aspirin and smoking on adenoma risk...
  79. ncbi Efficacy and tolerability of first-line triple therapy with levofloxacin and amoxicillin plus esomeprazole or rabeprazole for the eradication of Helicobacter pylori infection and the effect of CYP2C19 genotype: a 1-week, randomized, open-label study in Ch
    Xiaolin Pan
    Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    Clin Ther 32:2003-11. 2010
    ..Studies have reported that cytochrome P450 (CYP) 2C19 genotypes may affect the clinical efficacy of clarithromycinbased triple therapies, although there is only one report of such an effect with levofloxacin-based triple therapies...
  80. ncbi Update on the pharmacogenomics of proton pump inhibitors
    Krisztina Hagymasi
    Semmelweis University, II Department of Internal Medicine, 1088 Budapest, Szentkiralyi u 46, Hungary
    Pharmacogenomics 12:873-88. 2011
    ....
  81. ncbi Genotype-guided dosing of coumarin derivatives: the European pharmacogenetics of anticoagulant therapy (EU-PACT) trial design
    Rianne M F van Schie
    Utrecht University, Faculty of Science, Utrecht, The Netherlands
    Pharmacogenomics 10:1687-95. 2009
    ..The primary outcome measure is the percentage time in the therapeutic range for international normalized ratio. This report describes the design and protocol for the trial...
  82. pmc Polymorphic variants of cytochrome P450 2B6 (CYP2B6.4-CYP2B6.9) exhibit altered rates of metabolism for bupropion and efavirenz: a charge-reversal mutation in the K139E variant (CYP2B6.8) impairs formation of a functional cytochrome p450-reductase complex
    Haoming Zhang
    Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109 5632, USA
    J Pharmacol Exp Ther 338:803-9. 2011
    ..8 from forming a functional complex with CPR. Results from this work provide further insights to better understand the genotype-phenotype correlation regarding CYP2B6 polymorphisms and drug metabolism...
  83. ncbi Genetic polymorphism analysis of CYP2C19 in Chinese Han populations from different geographic areas of mainland China
    Lingling Chen
    Bio X Life Science Research Center, Shanghai Jiao Tong University, Hao Ran Building, Shanghai 200030, China
    Pharmacogenomics 9:691-702. 2008
    ..A comprehensive search for genetic polymorphisms of the CYP2C19 gene in the Chinese Han population has rarely been conducted. The present study was designed to determine the genetic basis of CYP2C19 polymorphisms...
  84. ncbi Esomeprazole 40 mg twice daily in triple therapy and the efficacy of Helicobacter pylori eradication related to CYP2C19 metabolism
    B S Sheu
    Department of Internal Medicine, Medical College, National Cheng Kung University, Tainan, Taiwan
    Aliment Pharmacol Ther 21:283-8. 2005
    ..To determine whether an increased dosage of esomeprazole 40 mg twice daily in triple therapy improved the Helicobacter pylori eradication rate for patients with different genotypes of S-mephenytoin 4'-hydroxylase (CYP2C19)...
  85. ncbi Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease
    Jessica L Mega
    TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    JAMA 306:2221-8. 2011
    ..Variants in the CYP2C19 gene influence the pharmacologic and clinical response to the standard 75-mg daily maintenance dose of the antiplatelet drug clopidogrel...
  86. ncbi Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction
    Yonghong Zhao
    Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, USA
    J Biol Chem 281:5973-81. 2006
    ..The results allow us to model the membrane-associated state of P450 and provide insight into how lipophilic substrates access the buried active site...
  87. ncbi Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site
    Guillaume A Schoch
    Department of Molecular and Experimental Medicine
    J Biol Chem 279:9497-503. 2004
    ..This novel finding identifies a peripheral binding site in P450s that may contribute to drug-drug interactions in P450 metabolism...
  88. ncbi Relation of genetic polymorphisms in the cytochrome P450 gene with clopidogrel resistance after drug-eluting stent implantation in Koreans
    Jung Myung Lee
    Division of Cardiology, Cardiovascular Genome Center, Yonsei University College of Medicine, Seoul, Republic of Korea
    Am J Cardiol 104:46-51. 2009
    ..In conclusion, CYP2C19*3 single-nucleotide polymorphisms is an independent risk factor of clopidogrel resistance in Korean subjects with coronary artery disease...
  89. ncbi Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite
    Miho Kazui
    Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co, Ltd, 1 2 58 Hiromachi, Shinagawa ku, Tokyo, 140 8710, Japan
    Drug Metab Dispos 38:92-9. 2010
    ..These results help explain the role of genetic polymorphism of CYP2C19 and also the effect of potent CYP3A inhibitors on the pharmacokinetics and pharmacodynamics of clopidogrel in humans and on clinical outcomes...
  90. ncbi Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study
    Huai Rong Luo
    Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, 66160 7417, USA
    Clin Pharmacol Ther 80:33-40. 2006
    ..Our objectives were to investigate cytochrome P450 (CYP) 2C19 polymorphism in Mexican Americans and compare the findings with those in 4 other ethnic groups...
  91. pmc Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin
    Sarah K Tate
    Department of Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT, United Kingdom
    Proc Natl Acad Sci U S A 102:5507-12. 2005
    ..Although the case made here is compelling, our results cannot be considered definitive or ready for clinical application until they are confirmed by independent replication...
  92. 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
    ..001). In conclusion, the maintenance warfarin dose can be estimated from demographic, clinical, and pharmacogenetic factors that can be obtained at the time of warfarin initiation...
  93. pmc Impact of the CYP2C19*17 allele on the pharmacokinetics of omeprazole and pantoprazole in children: evidence for a differential effect
    Gregory L Kearns
    Director, Pharmacogenetics Core Laboratory, Division of Clinical Pharmacology and Medical Toxicology, Children s Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA
    Drug Metab Dispos 38:894-7. 2010
    ..0001) and the apparent elimination rate constant (K(el); p = 0.0012); no significant genotype-phenotype relationships were observed for omeprazole...
  94. ncbi 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...
  95. pmc Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk
    Michelle Cotterchio
    Population Studies and Surveillance, Cancer Care Ontario, 620 University Avenue, Toronto, Ontario, Canada, M5G 2L7
    Cancer Epidemiol Biomarkers Prev 17:3098-107. 2008
    ....
  96. ncbi Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation
    H J Xie
    Division of Clinical Pharmacology, Department of Medical Laboratory Sciences and Technology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden
    Pharmacogenomics J 3:53-61. 2003
    ..Our results demonstrate that the polymorphic CYP2B6 is a major enzyme in the bioactivation of CPA. Moreover, we identified a strong impact of CYP2B6*6 on CPA 4-hydroxylation...
  97. ncbi A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin
    R J Ferguson
    National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
    J Pharmacol Exp Ther 284:356-61. 1998
    ..The two cDNAs were also used in an in vitro coupled transcription/translation assay. CYP2C19 protein was translated only from the CYP2C19*1 allele. These data indicate that CYP2C19*4 represents a new PM allele...
  98. 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...
  99. 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
    ..vitamin K epoxide reductase complex subunit 1-VKORC1). We hypothesized that variants in these two genes explain a substantial proportion of variability in stable warfarin dose and could be used as a basis for improved dosing algorithms...
  100. ncbi Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement
    Dirk Sibbing
    Deutsches Herzzentrum Munchen, Lazarettstrasse 36, 80636 München, Germany
    Circulation 121:512-8. 2010
    ..The aim of this study was to assess the impact of CYP2C19*17 on ADP-induced platelet aggregation, the risk of bleeding, and stent thrombosis in clopidogrel-treated patients undergoing percutaneous coronary intervention...
  101. ncbi Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents
    Dietmar Trenk
    Herz Zentrum Bad Krozingen, Bad Krozingen, Germany
    J Am Coll Cardiol 51:1925-34. 2008
    ....

Research Grants77

  1. CIGARETTE SMOKING OR PCBS EFFECTS ON ESTRADIOL
    Bao Ting Zhu; Fiscal Year: 1999
    ..6).Determine the effects of cigarette smoking on the concentration of unmetabolized estradiol in human uterine endometrium. ..
  2. Insecticide Resistance:CYP6D1 Regulation and Alleles
    Jeffrey Scott; Fiscal Year: 2005
    ..The ultimate goal of this research is to discover ways to delay the development of monooxygenase-mediated pyrethroid resistance. ..
  3. Pharmacogenetic Optimization of Anticoagulation Therapy
    Nita Limdi; Fiscal Year: 2007
    ..With the award of the K23 grant, structured training, guidance of mentors, environment and institutional support provided by the University, I will develop the skills necessary for a productive career in pharmacogenetics research. ..
  4. Novel noninvasive assessment of cytochrome P450 activity
    Evan Kharasch; Fiscal Year: 2009
    ..This approach may identify inter-individual variability in drug disposition and response;permit more individualized dosing, and reduces the cost of drug interaction studies. ..
  5. ANESTHETIC RENAL METABOLISM--MECHANISMS AND CONSEQUENCES
    Evan Kharasch; Fiscal Year: 2002
    ..More broadly, resulting biochemical and clinical insights will be applicable to the numerous other nephrotoxic haloalkenes that are ubiquitous environmental contaminants. ..
  6. MDR1 and Related Proteins during HIV PI Exposure
    David Greenblatt; Fiscal Year: 2005
    ..The findings will be of importance in understanding lipid disorders related to PIs as well as the kinetics of drugs used to treat HIV and related disorders. ..
  7. HAART Regimens in Substance Abusers
    David Greenblatt; Fiscal Year: 2003
    ....
  8. CHRONIC BENZODIAZEPINES: BEHAVIOR AND NEUROCHEMISTRY
    David Greenblatt; Fiscal Year: 2005
    ....
  9. GARLIC PREPARATIONS AND ANTIRETROVIRAL DRUGS
    David Greenblatt; Fiscal Year: 2004
    ..The work will provide immediately applicable clinical data on garlic interactions with antiretrovirals, as well as mechanistic data identifying the interaction process and its predictability from in vitro models. ..
  10. Metabolic Consequences of HAART: CYP3A and P-gp
    David Greenblatt; Fiscal Year: 2003
    ..This multidisciplinary proposal provides a clinical and scientific basis to assess the effects of currently available as well as experimental HAART medications on human CYP3A and P-gp. ..
  11. CYP3A Function in Aging AfricanAmericans
    David Greenblatt; Fiscal Year: 2006
    ..This study should provide important mechanistic information on the role of age, gender, and ethnicity as sources of variability in CYP3A-mediated drug metabolism and response. ..
  12. ANTIRETROVIRAL THERAPIES AND SUBSTANCE ABUSE
    David Greenblatt; Fiscal Year: 2002
    ..The in vitro model, if validated, has the potential to provide clinically important information on interactions involving HIV treatments and abusable drugs, at relatively low cost and with no human drug exposure. ..
  13. Treatment of Nicotine Dependence in Health Care Setting
    Gary Swan; Fiscal Year: 2009
    ....
  14. Biometric and Measured Genetic Research on Smoking
    Gary Swan; Fiscal Year: 2007
    ..Such knowledge will confer new insights about the etiology and progression of smoking and should improve the current understanding of smoking, which is still largely descriptive. ..
  15. CVD RISK FACTORS AND BRAIN MORPHOLOGY IN NHLBI TWINS
    Gary Swan; Fiscal Year: 2001
    ....
  16. Sphingolipid signaling in olfactory mucosa
    Mary Beth Genter; Fiscal Year: 2004
    ..abstract_text> ..
  17. Impact of Smoking Cessation on Sleep
    Gary Swan; Fiscal Year: 2008
    ..The results of this project will be particularly important for the development of targeted treatment approaches designed to ameliorate sleep disruption as part of an overall smoking cessation strategy. ..
  18. Beta-receptors and cardiovascular pharmacogenomics
    Julie Johnson; Fiscal Year: 2006
    ..abstract_text> ..
  19. Extracellular matrix in chloracetanilide carcinogenesis
    Mary Beth Genter; Fiscal Year: 2004
    ..abstract_text> ..
  20. Pharmacogenetics of ADRs: Warfarin Toxicity
    ALLAN EDWARD RETTIE; Fiscal Year: 2010
    ..abstract_text> ..
  21. PHARMACOKINETICS OF NICOTINE IN TWINS
    Gary Swan; Fiscal Year: 2002
    ..Ultimately, this knowledge may lead to more informed and more finely targeted treatment of individuals who are either susceptible to nicotine addiction or are already addicted to this substance. ..
  22. 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. ..
  23. Safety of Nicotine Reduction Strategy
    Neal Benowitz; Fiscal Year: 2009
    ..The proposed research is needed to guide governmental regulators as to how best to regulate nicotine in cigarettes and is an essential first step in examining the feasibility of a national regulation program. ..
  24. 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 ..
  25. MECHANISM OF INDUCTION OF OLFACTORY TUMORS BY ALACHLOR
    Mary Beth Genter; Fiscal Year: 2002
    ....
  26. 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. ..
  27. Active Site Models of CYP4 Enzymes
    ALLAN EDWARD RETTIE; Fiscal Year: 2010
    ..abstract_text> ..
  28. 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. ..
  29. Ontogeny of Drug Bioactivation and Idiosyncratic ADRs
    JAMES LEEDER; Fiscal Year: 2007
    ..abstract_text> ..
  30. VANDERBILT ADULT AIDS CLINICAL TRIALS UNIT
    David Haas; Fiscal Year: 2006
    ..The proposed ACTU will not only enroll patients into ACTG clinical trials, but will provide the ACTG the ability to address important questions concerning AIDS treatment and pathogenesis. ..
  31. Molecular Genetics of Cadmium Toxicity
    Daniel W Nebert; Fiscal Year: 2010
    ....
  32. SWAN Sleep Study II - Chicago (Rush) Site
    Howard Kravitz; Fiscal Year: 2008
    ..The results can inform primary prevention of adverse health outcomes due to the menopause-related sleep disturbances. ..
  33. PAHs: Balance of Detoxication vs Metabolic Activation
    Daniel Nebert; Fiscal Year: 2009
    ..dissemination of ingested BaP and will be informative in clinical studies in which we would determine which haplotypes of these three human genes might be associated with resistance vs. sensitivity to PAH-induced toxicity and cancer. ..
  34. Carcinogenicity of Estrogens
    DAVID SPINK; Fiscal Year: 2009
    ..These studies may elucidate roles of estrogen in the regulation of Ah responsiveness, CYP1 expression, and carcinogen bioactivation that may lead to novel breast cancer chemoprevention strategies. ..
  35. Mechanisms of Atypical Drug Kinetics and Interactions
    TIMOTHY TRACY; Fiscal Year: 2008
    ..From these data, computer models will be developed to predict the occurrence of atypical kinetics and potential drug interactions to assist in the drug development process. ..
  36. The Impact of HLA in Children Receiving HAART
    Akihiko Saitoh; Fiscal Year: 2008
    ..This research will also suggest modes of pathogenesis that can lead to the development of vaccine strategies. ..
  37. CNS Viral Dynamics and Cellular Immunity During AIDS
    David Haas; Fiscal Year: 2009
    ..Characterizing these relationships will expand our knowledge regarding key events that lead to AIDS dementia, and may suggest novel approaches to other immunologic or viral-mediated diseases that affect the brain. ..
  38. Pharmacokinetics & Genomics in Glomerular Diseases
    MELANIE JOY; Fiscal Year: 2008
    ..The selection of collaborators with expertise in the areas of this grant will enhance the career development of Dr. Joy. ..
  39. ETHANOL EFFECTS ON BONE FORMATION IN PREGNANCY
    Martin Ronis; Fiscal Year: 2006
    ..The role of CYP2E1 and free radicals in the skeletal toxicity of ethanol during these periods will also be studied. ..
  40. ETHANOL METABOLISM IN PREGNANCY--ROLE OF DIET
    Martin Ronis; Fiscal Year: 2005
    ....
  41. GENOTOXICITY IN CYP1A2 DEFICIENT TRANSGENIC MICE
    Daniel Nebert; Fiscal Year: 2002
    ..S. population. ..
  42. CLINICAL PHARMACOLOGY OF CHILDHOOD EPILEPSY
    Tracy Glauser; Fiscal Year: 2003
    ....
  43. PATHOGENESIS OF ANTICONVULSANT HYPERSENSITIVITY SYNDROME
    JAMES LEEDER; Fiscal Year: 2003
    ..It is anticipated that the basic experimental paradigm employed for these studies can also be applied to other idiosyncratic toxicities with suspected drug bioactivation and immune etiologies. ..
  44. Blood Genomics of Anticonvulsant Efficacy in Children
    Tracy Glauser; Fiscal Year: 2004
    ..We will study whole blood total RNA using the new human U133 Affymetrix oligonucleotide microarrays that assess over 39,000 transcripts. ..
  45. Pharmacogenetics and Antithrombotic Therapy
    Brian Gage; Fiscal Year: 2003
    ..Using high performance liquid chromatography, we will measure the levels of the 2 enantiomers of warfarin and test Hypothesis 4: Clearance of S-warfarin will be significantly decreased in the presence of 2C9 SNPs. ..
  46. CYP1A1 GENE AND ENVIRONMENTAL TOXICITY
    Daniel Nebert; Fiscal Year: 2005
    ..abstract_text> ..
  47. PharmGKB Experimental Biology Workshop 2005
    TIMOTHY TRACY; Fiscal Year: 2005
    ....
  48. Individual Promoter SNP and CpG Methylation Signatures
    SIMON SPIVACK; Fiscal Year: 2006
    ..abstract_text> ..
  49. Glutathione in Environmental Toxicity and Disease
    HOWARD SHERTZER; Fiscal Year: 2007
    ..Our proposed research should therefore help focus future genotype-phenotype association studies between the appropriate DNA variant sites in the GCLC and GCLM genes and disease. ..
  50. CYP2J2 Derived Eicosanoids and Endothelial Function
    Craig Lee; Fiscal Year: 2005
    ..abstract_text> ..
  51. Enhancing Tobacco Use Treatment for African American Light Smokers
    Lisa Sanderson Cox; Fiscal Year: 2010
    ....
  52. Change in Bone, Arthritis, Function: Hormones & Obesity
    MaryFran Sowers; Fiscal Year: 2009
    ....
  53. Hypocretin System Immune Diathesis in Human Narcolepsy
    John Black; Fiscal Year: 2004
    ..Long term objectives: This translational, multidisciplinary research will demonstrate fundamental insights into the cause of narcolepsy and will open avenues for new interventions and preventative measures for this debilitating disease. ..
  54. Comparison of CYP2 Genes Across Mammal Species
    Susan Hoffman; Fiscal Year: 2004
    ..abstract_text> ..
  55. Phytoestrogens and breast cancer risk
    Susan McCann; Fiscal Year: 2006
    ..These investigations, combining retrospective and experimental designs, as well as genetic analyses, will help to elucidate the role of dietary phytoestrogen intake in the etiology of a hormone- sensitive cancer. ..
  56. Mice with brain-specific deletion of the CPR gene
    Xinxin Ding; Fiscal Year: 2003
    ..abstract_text> ..
  57. CARCINOGENIC CYCLIC NITROSAMINE DNA ADDUCTS
    Stephen S Hecht; Fiscal Year: 2010
    ..The proposed research is significant because of the known human exposure to these carcinogens through the diet, tobacco products, and endogenous formation. ..
  58. CHEMOPREVENTIVE AGENTS AND HUMAN CYTOCHROME P450 IN VIVO
    GRANT WILKINSON; Fiscal Year: 2002
    ..Moreover, the information will be of value in the further development and evaluation of the efficacy/ toxicity of these new chemopreventive agent. ..
  59. Prediction of Drug-Drug Interactions
    Zeruesenay Desta; Fiscal Year: 2007
    ..The in vitro parameter estimates will be incorporated into our physiological pharmacokinetic models to test the predictive power and build a universal platform for complex interactions between chemicals. ..
  60. HMGB1/2 and Cellular Response to Fraudulent Nucleosides
    Evgeny Krynetskiy; Fiscal Year: 2007
    ..abstract_text> ..
  61. PHENYLACETATE--NOVEL THERAPEUTIC USES IN BREAST CANCER
    Neil Sidell; Fiscal Year: 2005
    ..Taken together, the information gained from these studies will provide a basic framework for the rationale use of PA analogs or similar acting compounds in the clinic. ..
  62. Functional Analysis of Optineurin in Glaucoma
    Mansoor Sarfarazi; Fiscal Year: 2007
    ..abstract_text> ..
  63. A Behavioral Economic Approach to Smoking Cessation
    Janet Audrain McGovern; Fiscal Year: 2007
    ..g., adolescents, older adults) and to other contexts (e.g., prevention). ..
  64. Longitudinal Patterns and Predictors of Smoking Behavior
    Janet Audrain McGovern; Fiscal Year: 2008
    ..Results from this study can be used to inform the timing, level, type, and specific target of smoking interventions. ..
  65. Mechanisms of Nicotine Induced Neurogenic Inflammation
    Kenneth Hargreaves; Fiscal Year: 2005
    ....
  66. Reducing Adverse Self-Medication Behaviors in Older Adults with Hypertension
    Patricia Neafsey; Fiscal Year: 2007
    ..Healthcare utilization will be compared between the 2 groups after 52 weeks and a cost-benefit analysis conducted. [unreadable] [unreadable] [unreadable]..
  67. Quality of Life of Testicular Cancer Survivors
    Yawei Zhang; Fiscal Year: 2008
    ..The increasing incidence of TC in young men, and the high survival rate, makes understanding the morbidity associated with TC survival a public health priority. [unreadable] [unreadable] [unreadable]..
  68. Nanoscale approaches to allelic silencing in myocardial disease states
    Euan Ashley; Fiscal Year: 2009
    ..This familial condition where the heart grows too thick is the most common cause of sudden death in young people and athletes. ..
  69. Mice with olfactory mucosa-specific Cre gene expression
    Xinxin Ding; Fiscal Year: 2003
    ..abstract_text> ..
  70. TCDD Impairs Prostate Development: Cyp2c39 & Retinoids
    CHAD VEZINA; Fiscal Year: 2008
    ..abstract_text> ..
  71. BIOBEHAVIORAL LUNG CANCER PREVENTION PROGRAM
    Caryn Lerman; Fiscal Year: 2004
    ..The long-term objective is to provide information necessary to match smoking cessation treatments to individuals, based on their genetic predispositions. ..
  72. THE ROLE OF MYCOBACTERIA IN CROHN'S DISEASE
    David Graham; Fiscal Year: 2005
    ..The results of this study should either confirm or refute the proposed etiologic association of M. paratuberculosis and Crohn's disease as well as the identification of patients with Crohn's disease and M. paratuberculosis. ..
  73. Longevity Genes in Founder Populations
    ALAN SHULDINER; Fiscal Year: 2005
    ..These advances will impact substantially on the health and quality of life of older Americans. ..
  74. Nicotine Intake in Smokers with Schizophrenia
    Jill Williams; Fiscal Year: 2009
    ....
  75. Nicotine Dependence Treatment in Psychiatric Comorbidity
    Jill Williams; Fiscal Year: 2005
    ..Techniques from dual diagnosis treatment can be adapted for treating nicotine dependence and include aspects of social skills training, motivational enhancement therapy and relapse prevention. ..
  76. Pregnane X Receptor: Regulation and Pharmacogenomics
    Erin Schuetz; Fiscal Year: 2007
    ..In total this proposal describes a comprehensive set of experiments to determine how PXR is regulated. ..