Clinics and Departments

Laboratory Services

Lab Dept:

Anatomic Pathology

Test Name:

CYTOCHROME P450 2C9 GENOTYPE SEQUENCING

General Information

Lab Order Codes:

2C9S

Synonyms:

P450 Genotyping

CPT Codes:

81227 – CYP2C9 gene analysis, common variants

Test Includes:

An interpretive report detailing the patient’s 2C9 phenotype and ability to metabolize drugs affected by CYP2C9.

Logistics

Test Indications:

Evaluating patients for adverse drug reactions involving fluoxetine. As an aid in altering dosing of antiepileptic drugs such as phenytoin.

Primary metabolism of many drugs is performed by cytochrome P450, a group of oxidative/dealkylating enzymes localized in the microsomes of many tissues including the intestines and liver. One of these CYP450 enzymes, CYP2C9, metabolizes a wide variety of drugs including warfarin and many nonsteroidal anti-inflammatory drugs. It is also partially responsible for metabolizing other drugs such as fluoxetine, fluvastatin, oral hypoglycemic drugs, and phenytoin.

CYP2C9-mediated drug metabolism is variable. Some individuals have altered CYP2C9 gene sequence that result in synthesis of enzyme devoid of catalytic activity or in enzyme with diminished catalytic activity. These individuals may metabolize various drugs at a slower rate than normal and may require dosing adjustments to prevent adverse drug reactions. However, CYP2C9 alleles with “reduced function” may metabolize different drugs at different rates, ranging from near normal to poor, but the literature is incomplete at this time.

Lab Testing Section:

Anatomic Pathology - Sendouts

Referred to:

Mayo Medical Laboratories (MML Test: 2C9/60528)

Phone Numbers:

MIN Lab: 612-813-6280

STP Lab: 651-220-6550

Test Availability:

Daily, 24 hours

Turnaround Time:

2 - 5 days

Special Instructions:

N/A

Specimen

Specimen Type:

Whole blood

Container:

Lavender top tube

Draw Volume:

3 mL (minimum: 0.3 mL) blood

Processed Volume:

Same as Draw Volume

Collection:

Routine venipuncture

Special Processing:

Lab Staff: Do Not centrifuge. Do Not freeze. Submit specimen in original collection container. Store and ship at room temperature.

Patient Preparation:

Transfusions will interfere with testing. Wait 4-6 weeks post-transfusion to draw. Bone marrow and liver transplants will also interfere with testing.

Sample Rejection:

Mislabeled or unlabeled specimens

Interpretive

Reference Range:

An interpretive report will be provided.

Drug-drug interactions and drug/metabolite inhibition must be considered when dealing with heterozyqous individuals and individual homozygous for the *2 allele.

Drug/metabolite

Limitations:

Direct DNA testing will not detect all known mutations that result in decreased or inactive CYP2D6. Absence of a detectable gene mutation or polymorphism does not rule out the possibility that a patient has an intermediate or poor metabolizer phenotype.

This test does not detect polymorphisms other than those listed. Gene duplications may occur by other mechanisms and may not be detected. Other polymorphisms in the primer binding regions can affect the testing, and ultimately, the genotyping assessments made. Testing may reflex to DNA sequencing to resolve difficult genotypes or to confirm interpretations.

Patients with an extensive or intermediate metabolizer genotype may have CYP2D6 enzyme activity inhibited by a variety of medications or their metabolites, including many tricyclic antidepressants (TCA’s), selective serotonin reuptake inhibitors (SSRI’s), many histamine H-2 receptor antagonists, amiodarone, celecoxib, cimetidine, cocaine, methadone, quinidine, and ritonavir, as well as several other drugs. Treatment with drugs that are inhibitors of CYP2D6, or produce inhibitors through metabolism, may generate a poor metabolizer phenotype in an individual who has an extensive or intermediate metabolizer genotype.

CYP2D6 alleles with “reduced function” may metabolize different drugs at different rates, ranging from near normal to poor but the literature on this is incomplete at this time.

The drug application that we currently that we currently support for testing and interpretation is for the treatment of depression and other psychiatric disorders.

This test is not for use in assessing for autoimmune hepatitis. Autoantibodies for CYP2D6 enzyme are found in many cases of autoimmune hepatitis.

Methodology:

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

References:

Mayo Medical Laboratories February 2013



  Lab Test Directory
    Chemistry
    Coagulation
    Flow/Immunology
    Hematology
    Microbiology/ Virology
    Other Fluids
    Pathology
    Serology
    Transfusion Services
    Urine/Stool

  Search Lab Test Directory
    List All Documents

  Lab Staff

  E-mail Lab Services