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
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