Cytochrome P450 2D6 Genotype, Saliva
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Identifying patients who are poor or extensive metabolizers of antidepressant drugs metabolized by CYP2D6
Adjusting dosages for antidepressant drugs that are metabolized by CYP2D6
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase Chain Reaction (PCR) with Allele-Specific Primer Extension (ASPE)/Bead Hybridization with Fluorescence Detection
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
CYP2D6 Genotype, Saliva
Treatment Resistant Depression Panel
Treatment Resistant Depression Panel
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple saliva genotype tests can be performed on a single specimen after a single extraction. See Multiple Saliva Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Oragene DNA Self-Collection Kit (Supply T651)
Specimen Volume: Full tube
1. Fill tube to line.
2. Send in original container per kit instructions.
1. Cytochrome P450 Patient Education Brochure (Supply T526) is available upon request.
2. Liver transplants will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions.
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Primary metabolism of many drugs is performed by cytochrome P450 (CYP), a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues including the intestines and liver. One of these CYP enzymes, CYP2D6, is wholly or partially responsible for the hydroxylation or dealkylation of many commonly prescribed drugs such as analgesics, anticonvulsants, antidepressants, antiemetics, antihypertensives, antiestrogens, antineoplastics, antipsychotics, antiretrovirals, antitussives, beta-blockers, cardioactive drugs, H-2 blockers, stimulants, and sympathomimetics. The current clinical application of this test is focused on the treatment of depression with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). Amitriptyline, clomipramine, desipramine, imipramine, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine are metabolized by CYP2D6.
CYP2D6-mediated drug metabolism is highly variable. Some individuals have altered CYP2D6 gene sequences that result in synthesis of enzyme devoid of catalytic activity, or in enzyme with diminished catalytic activity. These individuals metabolize SSRIs and TCAs poorly. Duplication of the functional CYP2D6 gene has been observed, which may result in ultrarapid metabolism of SSRIs and other drugs. Up to 13 copies of CYP2D6 have been reported.
Dosing of SSRIs and TCAs that are metabolized through CYP2D6 may require adjustment based on the individual patient's genotype. Patients who are poor metabolizers may require lower than usual doses to achieve optimal response. Patients who are ultrarapid metabolizers may benefit from increased doses. Patients with either ultrarapid or poor metabolism also may benefit by conversion to other comparable drugs that are not primarily metabolized by CYP2D6 or by therapeutic drug monitoring where applicable.
A number of specific polymorphisms have been found in the CYP2D6 gene that result in enzymatic deficiencies. The frequency of these polymorphisms varies within the major ethnic groups. CYP2D6 polymorphisms that produce poor metabolizers are found with frequencies of 7% to 10% in Caucasians, 2% in Africans and African Americans, and 1% in Asians. Individuals without inactivating polymorphisms, deletions, or duplications have the phenotype of an extensive drug metabolizer (normal) and are designated as CYP2D6*1/*1.
All of the identified polymorphisms associated with CYP2D6 are autosomal recessive. Consequently, only individuals who are homozygous or compound heterozygous for these polymorphisms are poor metabolizers. Individuals who are heterozygous, with 1 normal gene and 1 polymorphic gene, will have metabolism intermediate between the extensive (normal) and poor metabolizers.
The following information outlines the relationship between the polymorphisms detected in this assay and the effect on the activity of the enzyme produced by that allele:
Effect on Enzyme Metabolism
None (wild type)
Extensive metabolism (normal)
2850C->T and -1584C->G
100C->T and 1758G->A
Depends on the allele
duplicated (increased/no effect)
A complicating factor in correlating CYP2D6 genotype with phenotype is that many drugs or their metabolites are inhibitors of CYP2D6 catalytic activity. SSRIs, as well as some TCAs and other xenobiotics, may reduce or increase CYP2D6 catalytic activity. Consequently, an individual may require a dosing decrease greater than predicted based upon genotype alone. It is important to interpret the results of testing in the context of other coadministered drugs.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
An interpretive report will be provided.
Based on the test sensitivity and currently available CYP2D6 polymorphism carrier frequencies, persons of Caucasian descent who tested negative for the above polymorphisms would be estimated to have a <1.4% residual risk for carrying 1 or more copies of an undetected poor metabolizer allele. This residual risk may be higher or lower in other ethnic groups. The frequency of polymorphisms causing poor metabolism is highest in the Caucasian population and lower in African-Americans and Asians. Patients with an extensive (normal) or intermediate metabolizer genotype may have CYP2D6 enzyme activity inhibited by a variety of medications, or their metabolites. The following is a partial listing of drugs known to affect CYP2D6 activity as of the date of this report.
Drugs known to increase CYP2D6 activity:
Coadministration of these drugs will increase the rate of excretion of CYP2D6 metabolized drugs, reducing that drug's effectiveness.
Drugs known to decrease CYP2D6 activity:
Coadministration will decrease the rate of metabolism of CYP2D6-metabolized drugs, increasing the possibility of toxicity.
Drugs that undergo metabolism by CYP2D6:
Coadministration may decrease the rate of elimination of other drugs metabolized by of CYP2D6.
Drug-drug interactions and drug-metabolite inhibition or activation must be considered when dealing with heterozygous individuals. Drug-metabolite inhibition occurs frequently with selective serotonin reuptake inhibitors and tricyclic antidepressants, resulting in inhibition of residual functional CYP2D6 catalytic activity. Each report will include a list of commonly prescribed drugs, by drug class, that are known to alter CYP2D6 activity. This list includes only those drugs for which established, peer-reviewed literature substantiates the effect. The list provided is not all-inclusive.
CYP2D6 activity also is dependent upon hepatic and renal function status, as well as age. Patients also may develop toxicity if hepatic or renal function is decreased. Drug metabolism also is known to decrease with age. It is important to interpret the results of testing and dose adjustments in the context of renal and hepatic function and age.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Direct DNA testing will not detect all the known mutations that result in decreased or inactive CYP2D6. Absence of a detectable gene mutation or polymorphism does not rule out the possibility that a patient has an intermediate or poor metabolizer phenotype.
This test does not detect polymorphisms other than those listed. Gene duplications may occur by other mechanisms and may not be detected. Other polymorphisms in the primer binding regions can affect the testing, and ultimately, the genotyping assessments made. Testing may reflex to DNA sequencing to resolve difficult genotypes or to confirm interpretations.
Patients with an extensive or intermediate metabolizer genotype may have CYP2D6 enzyme activity inhibited by a variety of medications or their metabolites, including many tricyclic antidepressants, selective serotonin reuptake inhibitors, many histamine H-2 receptor antagonists, amiodarone, celecoxib, cimetidine, cocaine, methadone, quinidine, and ritonavir, as well as several other drugs. Treatment with drugs that are inhibitors of CYP2D6, or produce inhibitors through metabolism, may generate a poor metabolizer phenotype in an individual who has an extensive or intermediate metabolizer genotype.
CYP2D6 alleles with "reduced function" may metabolize different drugs at different rates, ranging from near normal to poor, but the literature on this is incomplete at this time.
The drug application that we currently support for testing and interpretation is for the treatment of depression and other psychiatric disorders.
This test is not for use in assessing for autoimmune hepatitis. Autoantibodies for CYP2D6 enzyme are found in many cases of autoimmune hepatitis. Order LKM/80387 Liver/Kidney Microsome Type 1 Antibodies, Serum for autoimmune hepatitis assessment.
If considering treatment with tamoxifen, order 2D6TO/60340 Cytochrome P450 2D6 Genotyping for Tamoxifen Hormonal Therapy, Saliva.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Bertilsson L, Dahl ML, 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. 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
3. Kirchheiner J, Brosen K, Dahl ML, et al: CYP2D6 and CYPSC19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages. Acta Psych Scand 2001 Sept;104(3):173-192
4. Lam YWF, 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
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from saliva. Direct polymorphism analysis for CYP2D6 gene is performed after (multiplex) PCR and allele-specific primer extension with Luminex Molecular Diagnostics’ proprietary Universal Tag sorting system on the Luminex 100 xMAP platform. A genotype is assigned based on the allele-specific fluorescent signals that are detected. (Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday, Thursday; 8 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81226-CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) (eg, drug metabolism), gene analysis, common variants (eg, *2, *3, *4, *5, *6, *9, *10, *17, *19, *29, *35, *41, *1XN, *2XN, *4XN)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|32895||2D6 Genotype Star Alleles||In Process|
|32896||2D6 Duplication||In Process|
|32897||2D6 Deletion||In Process|
|32898||2D6 -1584c>g (*2A)||In Process|
|32899||2D6 100c>t (*10)||In Process|
|32900||2D6 124g>a (*12)||In Process|
|32901||2D6 138inst (*15)||In Process|
|32902||2D6 883g>c (*11)||In Process|
|32903||2D6 1023c>t (*17)||In Process|
|32904||2D6 1707tdel (*6)||In Process|
|32905||2D6 1758g>t/a (*8/*14)||In Process|
|32906||2D6 1846g>a (*4)||In Process|
|32907||2D6 2549adel (*3)||In Process|
|32908||2D6 2613agadel (*9)||In Process|
|32909||2D6 2850c>t (*2)||In Process|
|32910||2D6 2935a>c (*7)||In Process|
|32911||2D6 2988g>a (*41)||In Process|
|32912||2D6 Genotype Interpretation||In Process|
|32913||2D6 Reviewed by||In Process|
|32914||2D6 Phenotype Interpretation||In Process|