CYP2D6

The cytochrome P450 (CYP) isozyme 2D6 is involved in the metabolism of many drugs. Variants in the gene that code for this enzyme may influence pharmacokinetics of the respective medications, and therefore may predict or explain nonstandard dose requirements, therapeutic failure, or adverse reactions.

For more information on pharmacogenetic testing, refer to the ARUP Consult Germline Pharmacogenetics - PGx topic.

Disease Overview

Treatment Issues

• The actual metabolic phenotype of a drug-metabolizing enzyme is subject to drug-drug interactions, clinical factors, and other nongenetic factors.
• Therapeutic drug monitoring and/or metabolic ratios may be useful for evaluating the pharmacokinetics of a particular drug for a particular patient.
• The Clinical Pharmacogenetics Implementation Consortium (CPIC)  and the Food and Drug Administration (FDA)  have published clinical associations and dosing guidelines involving CYP genotypes.

Genetics

Genes

CYP2D6

Inheritance

Autosomal codominant

Variants Tested

Variants or groups of variants, classified as star (*) alleles, are associated with predicted enzyme function, based on international consensus nomenclature. However, not all variants on a chromosome/allele are interrogated and assumptions about phase are made, as shown below. More details about nomenclature, allele frequencies, and phenotype predictions are available at PharmVar  or PharmGKB. 

Results

Results are reported according to the Results Reported and Clinical Significance table:

• When appropriate, genetic variant(s) detected are reported as star (*) alleles. Detailed nomenclature for each allele is included in the report.
• The detected combination of alleles (diplotype) is used to predict the metabolizer phenotype and, for CYP2D6, the activity score. These are included in the report.
• Phenotype predictions are subject to change as the scientific and clinical evidence evolves.
• No variants detected is predictive of *1 functional alleles and is reported as “Negative” or “Normal.”
• Functional variants without clinical indication or impact on clinical management may not be reported.

Limitations

• Only the targeted genetic variants will be detected by this panel. Assumptions about phase and content are made to assign alleles.
• Diagnostic errors can occur due to rare sequence variations.
• A combination of the CYP2D6*5 (gene deletion) and a CYP2D6 gene duplication cannot be specifically identified; however, this combination is not expected to adversely affect the phenotype prediction.
• The assay used to detect the CYP2D6*40 allele cannot distinguish between insertions of one or two copies; it also cannot distinguish between heterozygous and homozygous mutant samples due to unavoidable cross-reactivity with the wild type sequence. Additional assays will be used to help differentiate the CYP2D6*40 allele from other CYP2D6 star alleles.
• Risk of therapeutic failure or adverse reactions with gene substrates may be affected by genetic and nongenetic factors that are not detected by this test.
• The test result does not replace the need for therapeutic drug or clinical monitoring.