Cytochrome P450 2D6/2C19 Genotyping

CPT: 81225; 81226
Updated on 09/8/2024
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Synonyms

  • DME Genotyping

Expected Turnaround Time

7 - 10 days


Related Documents

For more information, please view the literature below.

Informed Consent for Genetic Testing

Pharmacogenomics Test List

For more information, please view the literature below.

Informed Consent for Genetic Testing

Pharmacogenomics Test List

For more information, please view the literature below.

Informed Consent for Genetic Testing

Pharmacogenomics Test List

For more information, please view the literature below.

Informed Consent for Genetic Testing

Pharmacogenomics Test List

For more information, please view the literature below.

Informed Consent for Genetic Testing

Pharmacogenomics Test List


Specimen Requirements


Specimen

Whole blood or Labcorp buccal swab kit (buccal swab collection kit contains 4 swabs and instructions for use of a buccal swab)


Volume

2 mL whole blood or one buccal swab kit (4 swabs)


Minimum Volume

1 mL whole blood or two buccal swabs


Container

Lavender-top (EDTA) tube or yellow-top (ACD) tube or Labcorp buccal swab kit


Collection

Collect specimen in a lavender-top (EDTA) or yellow-top (ACD) tube, or use a buccal swab kit (4 swabs). Ship whole blood specimen at room temperature or frozen. Ship buccal swab kit at room temperature.


Storage Instructions

Maintain whole blood specimen at room temperature or refrigerated for 28 days or frozen for 2 years. Maintain buccal swabs at room temperature for 2 months.


Stability Requirements

Temperature

Period

Room temperature

Whole Blood: 28 days

Swabs: 2 Months

Refrigerated

Whole Blood: 28 days

Swabs: Unstable

Frozen

Whole Blood: 2 years

Swabs: Unstable


Causes for Rejection

Quantity not sufficient for analysis; improper container; single buccal swab; wet buccal swab; buccal swabs without outer collection envelope; severely damaged buccal swab envelope; buccal swab envelope received open; frozen glass tube

Hemolysis; quantity not sufficient for analysis; improper container; single buccal swab; wet buccal swab; buccal swabs without outer collection envelope; severely damaged buccal swab envelope; buccal swab envelope received open; frozen glass tube

Quantity not sufficient for analysis; improper container; single buccal swab; wet buccal swab; buccal swabs without outer collection envelope; severely damaged buccal swab envelope; buccal swab envelope received open; frozen glass tube


Test Details


Use

Cytochrome P450 2D6 (CYP2D6) is a drug-metabolizing enzyme involved in the metabolism of more than 65 clinically important drugs including some antidepressants, anti-psychotics, opioids, beta-blockers, antiemetics, atomoxetine and tamoxifen. Individuals with some variant CYP2D6 alleles may experience a reduced therapeutic response and may be at risk for side effects from drugs that are metabolized by CYP2D6. CYP2D6 genotype information can be utilized to predict CYP2D6 metabolic phenotype, which can be used as an aid in determining a therapeutic strategy for drugs that are metabolized by CYP2D6. For example, CYP2D6 ultrarapid metabolizers may experience exaggerated side effects after the administration of codeine, while poor metabolizers may experience a reduced analgesic effect due to insufficient biotransformation into morphine. In these instances, alternative drugs may be considered.

Variation in the CYP2D6 gene can result in ultrarapid (UM), normal (NM), intermediate (IM) and poor (PM) drug-metabolizing phenotypes. Depending upon the genotype, a range between some of these phenotypes may be predicted by this assay. In general, relative to the *1 allele (normal function), *2, *35 and *53 alleles have normal function. *9, *10, *14, *17, *29, *41, *49 and *59 alleles have decreased function, while *3, *4, *5, *6, *7, *8, *11, *12, *13, *15, *31, *36, *40, *42 and *68 alleles have no function.

Cytochrome P450 2C19 (CYP2C19) is a drug-metabolizing enzyme involved in the metabolism of several clinically important drugs including the platelet aggregation inhibitor clopidogrel, the tricyclic antidepressants amitriptyline and nortriptyline, and the selective serotonin reuptake inhibitors citalopram and sertraline, and some proton pump inhibitors including omeprazole and pantoprazole. Individuals with some variant CYP2C19 alleles may experience a reduced therapeutic response and may be at risk for side effects from drugs that are metabolized by CPY2C19. CYP2C19 genotype information can be utilized to predict CYP2C19 metabolic phenotype, which can be used as an aid in determining a therapeutic strategy for drugs that are metabolized by CYP2C19. For example, the use of clopidogrel with an intermediate or poor metabolizer is associated with reduced platelet inhibition and an increased risk of cardiovascular complications, such as myocardial infarction, stroke, stent thrombosis and/or death, as compared with normal metabolizers. Ultrarapid metabolism is associated with an enhanced response to clopidogrel and increased risk of bleeding. In these instances, alternative drugs may be considered.

Variation in the CYP2C19 gene can result in ultrarapid (UM), rapid (RM), normal (NM), intermediate (IM), likely intermediate (LIM), poor (PM) and likely poor (LPM) drug-metabolizing phenotypes. In general, relative to the *1 allele (normal function), the *17 allele has increased function, *9 and *10 alleles have decreased function, while *2, *3, *4, *5, *6, *7, *8 and *35 alleles have no function.


Limitations

The exact effect of a particular genotype on individual drugs can vary. In addition to genotype, the metabolism of drugs may be influenced by additional factors that include environmental, dietary and other medications; these factors and others should be considered prior to initialing a new therapy. All results must be interpreted in the context of other test results and clinical findings. Results do not rule out the possibility of other variant alleles in CYP2D19 or other variant alleles in other drug metabolism pathways. Patients should speak with their healthcare provider about the individual results of this test.

Molecular-based testing is highly accurate, but as in any laboratory test, rare diagnostic errors may occur.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.


Methodology

DNA analysis is performed by allele-specific real-time polymerase chain reactions (RT-PCR) to detect single-nucleotide polymorphisms (SNPs), insertions or deletions (indels), hybrid, hybrid tandem and copy number variants (CNVs) within CYP2D6 gene and to assign variant CYP2D6 *2, *3, *4, *5 (deletion), *6, *7, *8, *9, *11, *12, *13 (hybrid), *13, *15, *17, *29, *31, *35, *36 (hybrid), *36+*10 (hybrid tandem), *40, *41, *42, *49, *53, *59 and *68 (hybrid) alleles and gene duplications (DUPS; copy number (CN) designated.). *1 denotes detection of the reference (wild-type) sequence at the assessed alleles. No other variants in this gene are detected by this assay.

Analysis for the *42 allele is dependent upon adequate DNA concentration.

DNA analysis is performed by allele-specific real-time polymerase chain reactions (RT-PCR) to detect single-nucleotide polymorphisms (SNPs) within the CYP2C19 gene and to assign variant CYP2C19 *2, *3, *4, *5, *6, *7, *8, *9, *10, *17 and *35 alleles. *1 denotes detection of the reference (wild-type) sequence at the assessed alleles. No other variants in this gene are detected by this assay.


References

Crews KR, Monte AA, Huddart R, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther. 2021 Oct;110(4):888-896.33387367
Hicks JK, Bishop JR, Sankuhl K, et al. Clinical pharmacogenetics implimentation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. 2015 Aug;98(2):127-134.25974703
Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017 Jul;102(1):37-44.27997040
Lee CR, Luzum JA, Sangkuhl K, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clin Pharmacol Ther. 2022 Nov;112(5):959-967.35034351
Lima JJ, Thomas CD, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing. Clin Pharmacol Ther. 2021 Jun;109(6):1417-1423.32770672
Pratt VM, Cavallari LH, Del Tredici AL, et al. Recommendations for Clinical CYP2D6 Genotyping Allele selection: a Joint Consensus Recommendation of the Association for Molecular Pathology, College of American Pathologists, Dutch Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association, and the European Society for Pharmacogenomics and Personalized Therapy. J Mol Diagn. 2021 Sep;23(9):1047-1064.34118403
US Food and Drug Adminstration (FDA). Table of Pharmacogenetic Associations. FDA website: https://www.fda.gov/medical-devices/precision-medicine/table-pharmacogenetic-associations. Accessed April 2023.

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