Test Catalog

Test ID: 2B6V    
Cytochrome P450 2B6 Genotype, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Aiding in determining therapeutic strategies for drugs that are metabolized by CYP2B6

 

Providing information relevant to bupropion, efavirenz, ketamine, methadone, and nevirapine, as well as other medications metabolized by CYP2B6

 

Determining the genotype if genotype-phenotype discord is encountered clinically after testing with a less comprehensive genotyping method has occurred

 

Identifying genotype when required for drug trials and research protocols

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The cytochrome P450 (CYP) family of enzymes is a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues including the intestines and liver. CYP2B6 is wholly or partially responsible for the metabolism of several commonly prescribed drugs.  

 

The CYP2B6 gene is highly variable with over 38 named alleles. The gene can have multiple sequence variations. Alleles thought to have an impact upon CYP2B6 enzyme function at the time that this test was developed are included in this test (See Table 1). Individuals without a detectable gene alteration will be reported as CYP2B6 *1/*1 but it is possible that these individuals harbor unknown variants that may impact metabolism. In addition, some individuals have genes that are hybrids of CYP2B6 and the CYP2B7 pseudogene. The frequency of these hybrids is unknown and this assay does not test for these hybrids.

 

Phenotyping was derived from the Pharmacogene Variation Consortium website,(1) an exhaustive review of the CYP2B6 literature, and the Clinical Pharmacogenetics Implementation Consortium website.(2) CYP2B6 genotype results are used to predict ultrarapid, rapid, normal (extensive), intermediate to normal (extensive), intermediate to rapid, intermediate, poor to intermediate, poor to normal, and poor metabolizer phenotypes. A CYP2B6 phenotype is predicted based upon the number of functional, partially functional, and nonfunctional alleles present in a sample. In rare instances, where alleles with unknown function are present in a homozygous or compound heterozygous state, an unknown phenotype occurs. 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.

 

Several medications act as substrates of CYP2B6. CYP2B6-metabolized medications with the highest quality of data for the impact of various CYP2B6 alleles on metabolism are: 

-Bupropion

-Efavirenz

-Ketamine

-Methadone

-Nevirapine

 

Other enzymes may be involved in the metabolism of these drugs. For example, bupropion is also metabolized by CYP2D6. Efavirenz is also metabolized by CYP2A6, although CYP2B6 is the major metabolizing enzyme Ketamine is also metabolized by CYP2A6, and nevirapine is also metabolized by CYP3A4 and CYP3A5. CYP2A6 testing is not available clinically at the time this document was written, but CYP2D6 (2D6CV / Cytochrome P450 2D6 [CYP2D6] Comprehensive Cascade), CYP3A4 (3A4V / Cytochrome P450 3A4 Genotype), and CYP3A5 (3A5V / CYP3A5 Genotype) testing is available.

 

There is a variable degree of substrate specificity exhibited by CYP2B6 alleles on these medications. This means that the same allele (ie, *6) may not metabolize all substrates at exactly the same rate.

 

Drugs that are metabolized by CYP2B6 may require dosage adjustment based on the individual patient's genotype. For example, patients who are poor metabolizers may require much lower than usual doses to achieve optimal response in the case of drugs that are inactivated by the CYP2B6 enzyme. Alternatively, patients who are ultrarapid metabolizers may benefit from increased doses in the case of drugs that are inactivated by CYP2B6 enzyme. In the absence of clear guidance from the FDA on dosing for various metabolizer phenotypes, patients with either ultrarapid or poor metabolism may benefit by switching to comparable alternate medications that are not primarily metabolized by CYP2B6, or by therapeutic drug monitoring where applicable.

 

Table 1. Enzyme Activity of Individual Star Alleles

Enzyme Activity

Examples of CYP2B6 star alleles

Normal (extensive) metabolism

*1, *5

Increased metabolism

*4, *22

Intermediate to normal activity

*7, *36

Decreased activity

*6, *8, *9, *11-*16, *18-*21, *26, *27

No or null activity

*28, *35, *38

Unknown activity

*23, *25

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.

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

 

The genotype, with associated star alleles, is assigned using standard allelic nomenclature as published by the Pharmacogene Variation (PharmVar) Consortium.(1)

 

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

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Rare variants may be present that could lead to false-negative or false-positive results.

 

Samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell, a pretransplant DNA specimen is recommended for testing.

 

Genetic test results in patients who have undergone liver transplantation may not accurately reflect the patient's genetic status for the genes on this panel.

 

This test is not designed to provide specific dosing recommendations and is to be used as an aid to clinical decision making only. Drug-label guidance should be used when dosing patients with medications regardless of the predicted phenotype.(3)

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Pharmacogene Variation Consortium database. Accessed 03/18/2018. Available at www.pharmvar.org/gene/CYP2B6

2. Clinical Pharmacogenetics Implementation Consortium website. Accessed 03/18/2018. Available at https://cpicpgx.org/

3. DAILYMED. U.S National Library of Medicine listing of FDA approved drug labels. Accessed 03/18/2018. Available at https://dailymed.nlm.nih.gov/dailymed/index.cfm

Special Instructions Library of PDFs including pertinent information and forms related to the test