| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Division of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky and UK Mental Health Research Center at Eastern State Hospital, Lexington, KY 40536.
2 Quintiles, Inc., Kansas City, MO 64137.
3 Affymetrix, Santa Clara, CA 95051.
4 Roche Molecular Systems, Inc. Alameda, CA 94501.
5 Department of Psychiatry, College of Medicine and University of Kentucky Mental Health Research Center at Eastern State Hospital, Lexington, KY 40508.
aAuthor for correspondence. Fax 859-257-7564; e-mail pjwedl1{at}uky.edu.
Background: There have been no published reports comparing the CYP450 GeneChip® microarray assay with more standard methods of genetic testing.
Methods: We collected 20-mL blood samples from 236 volunteers for DNA isolation and testing before each individual ingested 60 mg of dextromethorphan, and collected their urine. CYP2D6 alleles *3 to *7, *9, *17, and *41, and multiple CYP2D6 gene copies were tested by allele-specific PCR (AS-PCR), whereas alleles *2 to *4 and *6 to *11 were tested by the Affymetrix CYP450 GeneChip assay. Five of the CYP2D6 alleles (*3, *4, *6, *7, and *9) were tested by both AS-PCR and the CYP450 GeneChip assay in an independent and blinded fashion in 232 of the 236 healthy volunteers. The combined CYP2D6 genotype from both methods was used to divide the population into four subgroups, poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs), based on their relative function and ability to express the CYP2D6 gene. The urinary elimination of dextromethorphan was assessed in each of these CYP2D6 subgroups.
Results: The CYP2D6*3, *4, *6, *7, and *9 alleles showed a high degree of concordance between the CYP450 GeneChip and AS-PCR methods (>99% concordance). The mean (SD) of the log[dextromethorphan metabolic ratio (MR)] in the four CYP2D6 subgroups was PM = 0.49 (0.38); IM = -1.24 (0.53); EM = -2.35 (0.61); and UM = -2.43 (0.38).
Conclusions: Oligonucleotide microarray technology is an efficient and reliable way to test for CYP2D6 gene variation based on five alleles compared by separate methods. The methodology is influenced by the quality and amount of DNA present. The log(dextromethorphan MR) is a highly variable index that appears to reflect the crude nature of the dextromethorphan MR as an indicator of CYP2D6 in vivo enzyme activity.
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  K. J. Hogan, J. K. Burmester, M. D. Caldwell, Q. H. Hogan, D. B. Coursin, D. N. Green, R. M.R. Selzer, T. P. Broderick, D. A. Rusy, M. Poroli, et al. Perioperative Genomic Profiles Using Structure-Specific Oligonucleotide Probes Clin. Med. Res., September 1, 2009; 7(3): 69 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-J. Lee, S. S. Lee, H.-J. Jung, H.-S. Kim, S.-J. Park, C.-W. Yeo, and J.-G. Shin Discovery of Novel Functional Variants and Extensive Evaluation of CYP2D6 Genetic Polymorphisms in Koreans Drug Metab. Dispos., July 1, 2009; 37(7): 1464 - 1470. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-M. Yu, J. Qu, M. A. Felmlee, J. Cao, and X.-L. Jiang Quantitation of Human Cytochrome P450 2D6 Protein with Immunoblot and Mass Spectrometry Analysis Drug Metab. Dispos., January 1, 2009; 37(1): 170 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. de Leon, N. B. Sandson, and K. L. Cozza A Preliminary Attempt to Personalize Risperidone Dosing Using Drug-Drug Interactions and Genetics: Part II Psychosomatics, July 1, 2008; 49(4): 347 - 361. [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Kootstra-Ros, M. J. M. Van Weelden, J. W. J. Hinrichs, P. A. G. M. De Smet, and J. van der Weide Therapeutic drug monitoring of antidepressants and cytochrome p450 genotyping in general practice. J. Clin. Pharmacol., November 1, 2006; 46(11): 1320 - 1327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhen, O. Slanar, K. W. Krausz, C. Chen, J. Slavik, K. L. McPhail, T. M. Zabriskie, F. Perlik, F. J. Gonzalez, and J. R. Idle 3,4-Dehydrodebrisoquine, a Novel Debrisoquine Metabolite Formed from 4-Hydroxydebrisoquine That Affects the CYP2D6 Metabolic Ratio Drug Metab. Dispos., September 1, 2006; 34(9): 1563 - 1574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Li, R.-M. Pan, T. D. Porter, N. S. Jensen, P. Silber, G. Russo, J. A. Tine, J. Heim, B. Ring, and P. J. Wedlund NEW CYTOCHROME P450 2D6*56 ALLELE IDENTIFIED BY GENOTYPE/PHENOTYPE ANALYSIS OF CRYOPRESERVED HUMAN HEPATOCYTES Drug Metab. Dispos., August 1, 2006; 34(8): 1411 - 1416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. de Leon, S. C. Armstrong, and K. L. Cozza Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics, January 1, 2006; 47(1): 75 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. W. Go, C. T. H. Nguyen, D. M. Harris, and W.-N. Paul Lee Nutrient-Gene Interaction: Metabolic Genotype-Phenotype Relationship J. Nutr., December 1, 2005; 135(12): 3016S - 3020S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sistonen, S. Fuselli, A. Levo, and A. Sajantila CYP2D6 Genotyping by a Multiplex Primer Extension Reaction Clin. Chem., July 1, 2005; 51(7): 1291 - 1295. [Full Text] [PDF]
|
|
|
|
|
|
W. Steimer, K. Zopf, S. von Amelunxen, H. Pfeiffer, J. Bachofer, J. Popp, B. Messner, W. Kissling, and S. Leucht Amitriptyline or Not, That Is the Question: Pharmacogenetic Testing of CYP2D6 and CYP2C19 Identifies Patients with Low or High Risk for Side Effects in Amitriptyline Therapy Clin. Chem., February 1, 2005; 51(2): 376 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Steimer, K. Zopf, S. von Amelunxen, H. Pfeiffer, J. Bachofer, J. Popp, B. Messner, W. Kissling, and S. Leucht Allele-Specific Change of Concentration and Functional Gene Dose for the Prediction of Steady-State Serum Concentrations of Amitriptyline and Nortriptyline in CYP2C19 and CYP2D6 Extensive and Intermediate Metabolizers Clin. Chem., September 1, 2004; 50(9): 1623 - 1633. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
