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Test ID: 2D6O Cytochrome P450 2D6 Genotype, Saliva

Reporting Name

CYP2D6 Genotype, Saliva

Useful For

Determining the CYP2D6 genotype of patients considered for treatment with tamoxifen, codeine, and tramadol, as well as other medications metabolized by CYP2D6

 

Genotyping patients who prefer not to have venipuncture done

Specimen Type

Saliva


Specimen Required


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.

 

Supplies: DNA Saliva Collection Kit (T651: fees apply)

Specimen Volume: Full tube

Collection Instructions:

1. Fill tube to line.

2. Send in original container per kit instructions.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time
Saliva Ambient

Reference Values

An interpretive report will be provided.

Day(s) and Time(s) Performed

Monday, Thursday; 8 a.m.

Test Classification

This test was developed and its performance characteristics 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

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

Test ID Test Order Name Order LOINC Value
2D6O CYP2D6 Genotype, Saliva 40425-1

 

Result ID Test Result Name Result LOINC Value
35880 CYP2D6 Phenotype 72880-8
32895 CYP2D6 Star Alleles 40425-1
32914 CYP2D6 Interpretation 72880-8
32913 CYP2D6 Reviewed by No LOINC Needed

Clinical Information

The cytochrome P450 (CYP) family of enzymes is responsible for primary metabolism of many drugs. CYP450s are oxidative/dealkylating enzymes localized in the microsomes of many tissues including the intestines and liver. One of the CYP enzymes, CYP2D6, is wholly or partially responsible for the metabolism of many commonly prescribed drugs such as some analgesics, anticonvulsants, antidepressants, antipsychotics, antiemetics, antihypertensives, antiestrogens, antineoplastics, antipsychotics, antiretrovirals, antitussives, beta-blockers, cardioactive drugs, H-2 blockers, stimulants, sympathomimetic and other drug classes.

 

The CYP2D6 gene is highly variable with over 100 named alleles. The gene may be deleted, duplicated, and multiplied, and can have multiple sequence variations. In addition, some individuals have genes that are hybrids of CYP2D6 and the CYP2D7 pseudogene. Some individuals have altered CYP2D6 variants that result in synthesis of enzyme devoid of catalytic activity, or an enzyme with diminished catalytic activity. These individuals may process CYP2D6-metabolized medications more slowly depending upon the gene variant found on each chromosome. CYP2D6 duplications and multiplications involving active alleles may result in ultrarapid metabolism of CYP2D6-metabolized drugs. CYP2D6 genotype results are used to predict ultrarapid, ultrarapid to extensive (normal), extensive (normal), extensive (normal) to intermediate, intermediate, intermediate to poor, and poor metabolizer phenotypes for a sample.(see Table 1)

Table 1. Enzyme Activity of Individual Star Alleles

Enzyme Activity

Examples of CYP2D6* alleles

Normal (extensive) metabolism

*1, *35

Intermediate to normal activity

*2A

Decreased activity

*2, *9, *10, *14B, *17, *29, *41

No or null activity

*3, *4, *4N, *5, *6, *7, *8, *11, *12, *13, *14A, *15

 

CYP2D6 phenotype is predicted based upon the number of functional, partially functional, and nonfunctional alleles present in a sample.(see Table 2)

 

Table 2. Phenotype Assignment of CYP2D6

Predicted Drug Metabolizer Phenotype**

Without Gene Duplication

With Gene Duplication

UM

2 increased activity alleles

3 normal and/or increased activity alleles

EM to UM

A combination of 1 normal activity allele with 1 increased activity allele

A combination of 2 normal alleles with 1 decreased activity allele

EM

2 normal activity alleles; a combination of one increased activity allele with one decreased allele

A combination of 2 normal alleles with 1 null allele; a combination of 1 normal allele with 2 decreased activity alleles

IM to EM

 A combination of 1 normal activity allele with 1 decreased activity allele; a combination of 1 increased activity with 1 null allele

1 increased activity allele with 2 null alleles, 3 decreased activity alleles

IM

1 normal activity allele with 1 null activity allele; 2 decreased activity alleles

1 normal allele with 2 or more null alleles, 2 decreased activity alleles with 1 null allele.

PM to IM

A combination of 1 decreased activity allele with 1 null allele

1 decreased activity allele with 2 null allele

PM

Only null alleles detected

* Phenotyping was derived from the Human Cytochrome P450 (CYP) Allele Nomenclature Committee website and the PharmGKB website for the related Clinical Pharmacogenetics Implementation Consortium guidelines.

**Ultra-Rapid Metabolizer, UM; Extensive Metabolizer, EM; Intermediate Metabolizer, IM; Poor Metabolizer, PM

 

There are instances where a phenotype prediction is not categorical and, in these instances, a range of possible phenotypes will be given. It should be noted that other laboratories may use different phenotype prediction methods as there is no consensus on this at this time. However, the method used here represents the findings of the majority of literature available at this time. Individuals without a detectable gene alteration will have the predicted phenotype of an extensive drug metabolizer and are designated as CYP2D6*1/*1.

 

Dosing drugs that are metabolized by 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 in the case of drugs that are inactivated by the CYP2D6 enzyme, and higher than usual doses in the case of drugs that are activated by CYP2D6 enzyme. Alternatively, patients who are ultrarapid metabolizers may benefit from increased doses in the case of drugs that are inactivated by CYP2D6 enzyme, and lower doses in the case of drugs that are activated by CYP2D6. In the absence of clear guidance from FDA on dosing for various metabolizer phenotypes, patients with either ultrarapid or poor metabolism may benefit from therapeutic drug monitoring or switching to another comparable drug that is not primarily metabolized by CYP2D6.

Interpretation

An interpretive report will be provided.

 

All alterations detected will be reported with standard allelic nomenclature as published by the Human Cytochrome P450 (CYP) Allele Nomenclature Database Committee (www.cypalleles.ki.se/CYP2D6.htm). Novel variants will be classified based on known, predicted, or possible effect on gene function and reported with interpretive comments detailing their potential or known significance.

 

For additional information regarding pharmacogenomic genes and their associated drugs, please see the Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

2. Human Cytochrome P450 (CYP) Allele Nomenclature Database. Accessed September 21, 2015. Available at www.cypalleles.ki.se/cyp2d6.htm

3. Black JL 3rd, Walker DL, O'Kane DJ, Harmandayan M: Frequency of undetected CYP2D6 hybrid genes in clinical samples: impact on phenotype prediction. Drug Metab Dispos 2012;40(1):111-119

4. Goetz MP, Rae JM, Suman VJ, et al: Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 2005;23:9312-9318

5. Kirchheiner J, Nickchen K, Bauer M, et al: Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004;9:442-473

6. Crews KR, Gaedigk A, Dunnenberger HM, et al: Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther 2012 Feb;91(2):321-326

7. Hicks JK, Swen JJ, Thorn CF, et al: Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther 2013 May:93(5):402-408

Analytic Time

2 days (not reported Saturday or Sunday)

Method Name

Polymerase Chain Reaction (PCR) with Allele-Specific Primer Extension (ASPE)/Bead Hybridization with Fluorescence Detection

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.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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