Cytochrome P450 2D6/2C19 Genotyping

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

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

1 mL whole blood or two buccal swabs

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

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.

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.

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.