- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 1 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Characteristics: Impaired drug metabolism causing adverse drug reactions or lack of drug response. Drugs metabolized by CYP2C19 include clopidogrel, S-mephenytoin, diazepam, R-warfarin, some antidepressants (eg, citalopram, amitriptyline, clomipramine), proton pump inhibitors (eg, omeprazole, lansoprazole), and antimalarials (eg, chloroguanide).
Inheritance: Autosomal recessive.
Cause: CYP2C19 allelic variants.
Negative: No variants detected is predictive of *1 functional alleles and normal enzymatic activity.
Variants Tested: (Variants are numbered according to NM_000769 transcript).
Decreased function: *9 (c.431G>A); *10 (c.680C>T).
Non-functional: *2 (c.681G>A), *3 (c.636G>A), *4 (c.1A>G), *6 (c.395G>A), *7 (c.819+2T>A), *8 (c.358T>C).
Increased function: *17 (c.-806C>T; increased gene transcription).
Incidence of Poor Metabolizer Phenotype: 4 percent of Caucasians, 5 percent of African Americans, and up to 25 percent of Asians.
Penetrance: Drug dependent.
Clinical Sensitivity: 99 and 87 percent of clinically significant variants detected in Asians and Caucasians respectively; sensitivity is unknown in other ethnicities.
Methodology: Polymerase chain reaction, DNA hybridization, and electrochemical detection.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Only the targeted CYP2C19 variants will be detected. Variants in other genes will not be detected. Diagnostic errors can occur due to rare sequence variations. Variant detection is not a substitute for therapeutic drug monitoring or other clinical monitoring.
References: Overview of CYP (http://www.anaesthetist.com/physiol/basics/metabol/cyp/Findex.htm); nomenclature of CYP alleles (http://www.cypalleles.ki.se/); drug substrates/inhibitors/inducers for CYP (http://medicine.iupui.edu/clinpharm/ddis/clinical-table/).
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|0051411||CYP2C19 Predicted Phenotype||62365-2|
- Cytochrome P450 2C19 Genotype by Sequencing Analysis, Saliva
- P450 2C19 Genotyping
- Treatment Resistant Antidepressant Panel