Cytochrome P450 2C19 (CYP2C19) 9 Mutations FOR DETECTION OF CYP2C19 MUTATIONS AFFECTING DRUG
concentrations of the parent drug and slower clearance. Carriers
of CYP2C19*17 may exhibit lower plasma concentrations
• Cytochrome P450 2C19 (CYP2C19) is an isoenzyme of the
and higher clearance. Therapeutic drug monitoring should be
cytochrome P450 super family that metabolizes and eliminates
common prescription drugs, including anti-convulsants, anti-
◦ Tamoxifen (Nolvadex®): Carriers of CYP2C19 *17 have
depressants, proton pump inhibitors, and antithrombotics
been shown to produce higher concentrations of the active
(clopidogrel/Plavix®), as well as chemotherapy, anti-malaria, and
metabolite endoxifen and experience decreased breast cancer
recurrence when treated with tamoxifen. Decrease function
alleles (e.g., CYP2C19 *9) are not expected to affect response
• Pharmacogenetic variation leads to inappropriate concentrations
of drugs and drug metabolites, which may contribute to toxicity
and risk of adverse drug reactions or lack of therapeutic benefit.
• For individuals with a personal or a family history of adverse
drug reactions to medications metabolized by CYP2C19.
• Metabolizer phenotypes can be predicted by the CYP2C19 Interpretation
• The clinical impact of the CYP2C19 genotype is influenced by
whether a drug is activated (e.g., clopidogrel, tamoxifen) or
• If no CYP2C19 mutations are detected, this suggests *1 alleles
inactivated (e.g., amitryptiline, escitalopram) by CYP2C19,
involvement of other metabolic pathways, and other non-genetic
• If one decreased function or one non-functional CYP2C19
factors (e.g., concomitant medications).
mutation is detected, intermediate-to-normal CYP2C19Epidemiology
• If two decreased function alleles, or one decreased function and
• CYP2C19 mutation frequency is dependent on ethnicity. The
one non-functional allele are detected, intermediate CYP2C19
most common mutations are represented by the *2 and *3 alleles.
• The *2 allele is found in approximately 30% of Asians and 15%
• If two non-functional mutations are present on opposite alleles,
this predicts low CYP2C19 enzymatic activity and a poor
• The *3 allele is present in approximately 8% of Asians and is rare
(less than 1%) in Caucasians and African-Americans.
• Heterozygosity or homozygosity for the increased function *17
allele is associated with increased CYP2C19 activity and an
• A poor metabolizer phenotype (caused by two non-functional
CYP2C19 alleles) is present in 4% of Caucasians, 5% of African-
• Genotype results should be interpreted in the context of the
individual clinical situation. Consultation with a clinical
pharmacy professional is recommended.
• The CYP2C19 gene has nine exons and is located on chromosome
• Polymerase chain reaction (PCR) followed by detection primer
• Inheritance is autosomal recessive.
Indications for Ordering Nucleotide Mutation Predicted Designation Change
• Pre-therapeutic testing to identify individuals who should avoid,
or may require unconventional doses of medications metabolized
◦ Clopidogrel (Plavix®): Carriers of CYP2C19 *2 or *3 alleles
have been shown to respond poorly to standard doses due to
reduced metabolic activation of the drug. An alternate drug or
dose escalation, coupled with monitoring of platelet function,
◦ Amitriptyline (Elavil®) and escitalopram (Lexapro®): Carriers
of CYP2C19 *2 or *3 alleles may exhibit higher plasma
2012 ARUP LABORATORIES. ALL RIGHTS RESERVED. JANUARY 2012
500 Chipeta Way, Salt Lake City, UT 84108 | (800) 522-2787 | (801) 583-2787 | |
ARUP is an enterprise of the University of Utah and its Department of Pathology.Nucleotide Mutation Predicted
• Drug metabolism may be affected by non-genetic factors. Designation Change
• Mutation detection is not a substitute for therapeutic drug or
• Rare diagnostic errors may occur due to primer-site mutations. Related Tests
• Cytochrome P450 2C9 (CYP2C9) 2 Mutations ()
• Cytochrome P450 2D6 (CYP2D6) 14 Mutations & Gene
1. Goldstein JA and de Morais SM. Biochemistry and molecular
biology of the human CYP2C subfamily. Pharmacogenetics
2. Streetman DS, Bertino JS, Jr., and Nafziger AN. Phenotyping
of drug-metabolizing enzymes in adults: a review of in-vivo
cytochrome P450 phenotyping probes. Pharmacogenetics
3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug
• Clinical sensitivity is estimated at 99% and 87% for Asians
Interaction Table. Indiana University School of Medicine (2007).
and Caucasians, respectively; sensitivity is unknown in other
http://medicine.iupui.edu/clinpharm/ddis/table.asp. (accessed on
• Analytical sensitivity and specificity are 99%.
4. Mega JL, et al. Cytochrome p-450 polymorphisms and response
to clopidogrel. N Engl J Med 2009;360(4):354–362.
5. Simon T, et al. Genetic determinants of response to clopidogrel
and cardiovascular events. N Engl J Med 2009;360(4):363–375.
• CYP2C19 mutations, other than those listed above, are not
• Mutations in other genes associated with drug metabolism or
For specific collection, transport, and testing information, refer to the ARUP website at . For information on test selection, ordering, and interpretation, refer to ARUP Consult® at
ARUP LABORATORIES | JANUARY 2012
for Security Sector Transformation “G.S. Rakovski” Defence and Staff College, Sofia, Bulgaria ABSTRACT: Advanced approaches towards defence management, and the process of the ongoing force transformation in particular, rely to a great extent on Capabilities-Based Planning (CBP) to provide for robust response to a broad spectrum of threats and challenges. Our assumption is that CBP has
Cannabis has been promoted in the United States over the last 20 years as a means of relieving a wide range of conditions. It is said to provide relief for chronic states of pain, loss of appetite in the case of aids patients and cancer sufferers, nausea and vomiting (as a result of chemotherapy), asthma, glaucoma (increased internal pressure on the eye) and for sufferers of multiple scleros