Cytochrome P-450 2D6 Genotyping
 

DESCRIPTION - DNA Mutation Analysis, Genotyping and Scanning Analysis

Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic metabolizing liver enzyme of the cytochrome P450 super family involved with the metabolism and elimination of many commonly prescribed drugs (24%) including the selective serotonin reuptake inhibitors (SSRI), tricylic antidepressants (TCA), betablockers such as Inderal and the Type 1A antiarrhythmics. Approximately 10% of the population has a slow acting form of this enzyme and 7% a super-fast acting form. Thirty-five percent are carriers of a non-functional 2D6 allele, especially elevating the risk of ADRs when these individuals are taking multiple drugs. Drugs that CYP2D6 metabolizes include Prozac, Zoloft, Paxil, Effexor, hydrocodone , amitriptyline, Claritin, cyclobenzaprine, Haldol, metoprolol, Rythmol, Tagamet, tamoxifen, and the over-the-counter diphenylhydramine drugs, Allegra, Dytuss, and Tusstat. CYP2D6 is responsible for activating the pro-drug codeine into its active form and the drug is therefore inactive in CYP2D6 slow metabolizers.

Test Order Code CYP2D6
CPT Codes
 		 83891 x 1, 83892 x 6, 83894 x 3, 83898 x 5, 83900 x 2, 83914 x 13, 83909 x 2, 83912 x 1
Indications For Testing

  • Detecting genetic variations in drug-metabolizing enzymes is useful for identifying individuals who may experience adverse drug reactions with conventional doses

  • Recommended for individuals requiring drug efficacy, dosage tolerance and metabolic assessment for single or multiple drug interactions.

Turn Around Time

 Up to 5 days. Expedited analysis is available upon request for an additional charge.

Specimen Requirements

Peripheral Blood
All peripheral blood collections require Purple/Lavender-top (EDTA) vaccutainer tubes.

  • Adults: 2 tubes each with 7.5 mL whole blood

  • Children & Infants: 1 tube of 5-6 mL whole blood

  • Keep samples at ambient temperature and ship by overnight courier to arrive at the Molecular Laboratory within 24 hrs after collection of the specimen. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature.
Specimen Kits

DNA Specimen Collection Kits can be obtained from Transgenomic Molecular Laboratory.

Shipping and Contact Information Transgenomic Molecular Laboratory
12325 Emmet Street Omaha, NE 68164 USA
Phone: (866) 500-GENE / (866) 500-4363 Fax: (402) 452-5447
E-mail: labservice@transgenomiclabs.com
Test Submission  and Patient Consent Forms

Due to the unique nature of genetic testing, patients should receive pre-test and post-test counseling. Informed consent is recommended.

Test Methodology

Scanning and sequence analysis of alleles 2 and 3.

Sensitivity The sensitivity and specificity for detection of each these mutations is 99.9%.
Limitations This assay is specific for the alleles and nucleotides indicated only. Other mutations within these genes or other genes that affect drug metabolism will not be detected; consequently, such mutations cannot be ruled out.
References
  1. Bertilsson, L., Dahl, M.L., Dalen, P., Al-Shurbaji, A.: Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br. J. Clin. Pharmacol. 2002 Feb;53(2):111-122
  2. Bradford, L.D. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002 Mar;3 (2):229-43.
  3. Brockmoller, J. et.al. Pharmacogenetic diagnosis of cytochrome P450 polymorphisms in clinical drug development and in drug treatment. Pharmacogenetics. 2000:1:125-51.
  4. Cozza, K.L., Armstrong SC, Oesterheld JR (2003) Drug Interaction principles for Medical Practice. American Psychiatric Publishing Inc
  5. Kirchheiner, J., Nickchen, K., Bauer, M., Wong, M.L., Licinio, J., Roots, I., Brockmoller, J. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry. 2004 May;9(5):442-73.
  6. Kirchheiner, J., Brosen, K., Dahl, M.L., et al.: CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta. Psych. Scand. 2001 Sept;104(3):173-192
  7. Lam, Y.W.F., Gaedigk, A., Ereshefsy, L., et al: CYP2D6 inhibition by selective serotonin reuptake inhibitors: analysis of achievable steady-state plasma concentrations and the effect of ultrarapid metabolism at CYP2D6. Pharmacotherapy 2002;22:1001-1006
  8. Linder, M.W. and Valdes, R.Jr. Pharmacogenetics in the Practice of Laboratory Medicine. Molecular Diagnosis. 1999;4:365-79
  9. Lundqvist, E., Johansson, I., Ingelman-Sundberg, M.: Genetic mechanisms for duplication and multiduplication of the human CYP2D6 gene and methods for detection of duplicated CYP2D6 genes. Gene 1999 Jan 21;226(2):327-338
  10. Marez, D., Legrand, M., Sabbagh, N., Guidice, J.M., Spire, C., Lafitte, J.J., Meyer, U.A., Broly, F. Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics. 1997 Jun; 7(3):193-202.
  11. Shulman, R.W., Ozdemir, V. Psychotropic medications and cytochrome P450 2D6: pharmacokinetic considerations in the elderly. Can. J. Psychiatry. 1997; 42 Suppl 1:4S-9S.
  12. Zackrisson, A.L., Lindblom, B. Identification of CYP2D6 alleles by single nucleotide polymorphism analysis using pyrosequencing. Eur J Clin. Pharmacol. 2003; 59 (7):521-6.
Note: The performance characteristics of this test were validated by TRANSGENOMIC Molecular Laboratory. The U.S. Food and Drug Administration (FDA) has not approved this test. However, FDA approval is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. TRANSGENOMIC Molecular Laboratory is authorized under Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity testing.