Report Contents

  1. Coriell Personalized Medicine Collaborative Research Study Report. This report includes all data included in the clinical report as well as supplemental drug specific interpretations and educational material.
  2. Clinical Report. This report was generated and approved by Coriell’s CLIA certified genotyping laboratory.

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Coriell Institute for Medical Research
403 Haddon Avenue
Camden, New Jersey 08103 USA
Phone: 888-580-8028
Fax: 856-964-0254
cpmc.coriell.org
CPMC Research Study Report
Name: NATALIE DEMO
Date of Birth:
Coriell ID: DEMONAT
Lab Accessioning Number: DEMONAT
Ordering Physician:
Gender: Female
Date Collected:
Date Received:
Date of Report: 04/29/2011

CYP2C19 and clopidogrel (Plavix®) Response

These results were generated in a CLIA-approved laboratory as part of the Coriell Personalized Medicine Collaborative research study. Results take into account 8 genetic variants in the CYP2C19 gene, known to contribute to the metabolism of clopidogrel (Plavix®). This report reflects this participant’s metabolism status predicted based on genetic testing but does not reflect whether they are currently taking clopidogrel (Plavix®).

The CPMC has genetic counselors and pharmacists available to assist with report interpretation at no charge. For questions please contact us at cpmcgc@coriell.org or by phone at 888-580-8028. Participants may schedule an appointment with one of our board-certified genetic counselors or pharmacists by logging into their web portal account and clicking on "request an appointment". For general information about the CPMC please visit our website cpmc.coriell.org.

This research report includes all data included in the clinical report as well as supplemental drug specific interpretations and educational material. Please see the report that follows for the official clinical report.

Your Genetic Result

CPMC tested multiple sites of genetic variation within the CYP2C19 gene that affect the way the body responds to clopidogrel.

Your combination of genetic variant results (listed below in yellow) is commonly referred to as:

CYP2C19*4/*4 (Clopidogrel Poor Metabolizer)

VARIANTS TESTEDYOUR RESULTREFERENCE VALUE
rs12248560 CC C C
rs28399504 GG A A
rs41291556 TT T T
rs72558184 GG G G
rs4986893 GG G G
rs4244285 GG G G
rs72558186 TT T T
rs56337013 CC C C

Other variants, not currently included in this CPMC test may influence this result and interpretation.

Interpretation of Your Results

Clopidogrel Poor Metabolizer
also called CYP2C19*4/*4
  • Poor metabolizers have significantly decreased CYP2C19 activity.
  • Poor metabolizers are not likely to benefit from taking clopidogrel and may be at increased risk for blood clots, heart attack or stroke.
  • Talk to your doctor about alternative medications.
  • This result may also affect your response to other medications. For more information on other medications that are affected by the CYP2C19 gene, click here.

What is Clopidogrel (Plavix®)?

Clopidogrel is an anti-platelet medication.

This medication is used to prevent platelets, a type of cell found in the blood, from clumping together. When platelets clump together they can form clots which block the flow of blood.

Uses:

  • To treat acute coronary syndrome (decreased blood flow to the heart) and peripheral artery disease (poor circulation in the legs)
  • To prevent stroke, heart attack, and formation of blood clots after stent placement
Risk Factors Affecting Response to Clopidogrel

Genetic Risk Factors

Genetic variants, or changes, in a gene called CYP2C19 can affect the way your body metabolizes clopidogrel.

Some people with certain genetic variants may not benefit as much from taking clopidogrel compared to people without these variants. These people can be at increased risk for heart attacks or blood clots.

Non-Genetic Risk Factors

Many factors affect how your body responds to medications.

Non-genetic factors include: diet, lifestyle, medical history and interactions between medications.

Genetic Risk Factors

Some medications are metabolized (broken down or activated) by enzymes. Variants in the genes coding for these enzymes may cause your body to metabolize a medication more quickly or more slowly than normal. This change can affect how well the medication works, as well as the risk of side effects.

Genes Affecting Clopidogrel Metabolism:

CYP2C19

Types of Variants in CYP2C19

There are many variants in the CYP2C19 gene. A number system has been created to name common combinations of variants. Some variant combinations have not been assigned a number yet. Other combinations of variants cannot be assigned a number with certainty. We all have 2 copies of every gene; when possible, you will have a CYP2C19 result with two numbers.

Example: CYP2C19 *1/*2

Types of Clopidogrel Metabolizers

Each result is associated with a metabolizer status which describes how the enzyme is working.



Example: intermediate metabolizer

Your personal result can be found by clicking on the RESULTS tab.

How Common

The table and picture below show the different types of clopidogrel metabolizers and how common each is in the African Ancestry population.

Reduced CYP2C19 activity

Poor Metabolizer

3 out of 100 people

Not likely to receive full benefit of clopidogrel. Increased risk for heart attack and stroke.

Intermediate Metabolizer

20 out of 100 people

May not receive full benefit of clopidogrel. Possible increased risk for heart attack and stroke.
Typical CYP2C19 activity

Extensive Metabolizer

29 out of 100 people

Expected to benefit from standard clopidogrel dose.
Increased CYP2C19 activity

Ultra-Rapid Metabolizer

38 out of 100 people

Expected to process medication more quickly. Possible increased benefit. Possible increased risk for bleeding.
Uncertain CYP2C19 activity

Metabolizer Status Unknown

10 out of 100 people

Not enough data to determine clopidogrel response.

Drug-Drug Interactions

In addition to your genes, other medications may affect how your body metabolizes clopidogrel and may increase the risk of side effects or prevent clopidogrel from working effectively.

The following medications, when taken with clopidogrel, may reduce the benefit of clopidogrel or increase the risk for side effects:

MedicationAlso Known As
Omeprazole Prilosec, Zegerid
Warfarin Coumadin, Athrombin
Nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, ibuprofen, acetaminophen, naproxen

For a selected list of other medications that can also affect your response to clopidogrel, click here.

Share these results with your healthcare providers.

Print Report

DO NOT MAKE CHANGES TO ANY MEDICATION WITHOUT TALKING TO YOUR HEALTHCARE PROVIDERS.


Result Limitations

  • This result alone does NOT predict your total response to clopidogrel.
  • Other factors such as body weight, various health conditions, and other medications may impact an individual’s response to clopidogrel.
  • There may be other genetic variants within the CYP2C19 gene which influence response to clopidogrel but are not included in this test.
  • There may be other genetic variants in the CYP2C19 gene for which response to clopidogrel has not been documented and/or validated in multiple studies.
  • There may be genetic variants in other genes that influence response to clopidogrel.
  • This result reflects published data available at the time this gene-drug pair was approved by the CPMC Informed Cohort Oversight Board (12-8-10). The information provided may change as new scientific information becomes available.
  • Although rare, it is possible that you may receive an incorrect result; 100% accuracy of reported results cannot be guaranteed.
  • Occasionally there may be a specific variant on a gene chip that is not able to be read or interpreted. In this case you will not receive a result for that variant. It is expected that you will receive results for about 95% of variants approved by the Pharmacogenetics Advisory Group (PAG) and Informed Cohort Oversight Board (ICOB).
  • Every effort will be made to provide you with risk information based on your reported race/ethnicity. However, data may not be available for all races/ethnicities. Please see your individual results to determine which race/ethnicity the data is based on.

Test Limitations

DNA-based testing is highly accurate, however there are many sources of potential error including: mis-identification of samples, rare technical errors, trace contamination of PCR reactions, and rare genetic variants that interfere with analysis. This test or one or more of its components was developed and its performance characteristics determined by the Coriell Institute for Medical Research. It has not been approved by the Food and Drug Administration (FDA). The FDA has determined that such approval is not necessary. The Coriell Institute is regulated under the Clinical Laboratory Improvement Amendments (CLIA) of 1988 as qualified to perform high-complexity testing.

Methods

References
  • Chen BL, et al. Clin Exp Pharmacol Physiol.2008;35(8):904‐8.
  • Collet JP, et al. The Lancet. 2009;373(9660):309‐317.
  • Ferguson RJ, et al. J Pharmacol Exp Ther. 1998;284(1):356‐61.
  • Giusti B, et al. Am J Cardiol. 2009; 103(6):806–811.
  • Gladding P, et al. JACC Cardiovasc Interv. 2008;1(6):620‐7.
  • Ibeanu GC, et al. Pharmacogenetics. 1998;8(2):129‐35.
  • Ibeanu GC, et al. J Pharmacol Exp Ther. 1998;286(3):1490‐5.
  • Ibeanu GC, et al. J Pharmacol Exp Ther. 1999;290(2):635‐40.
  • Mega JL, et al. N Engl J Med. 2009;360(4):354‐62.
  • Mega JL, et al. JAMA. 2010;304; 1821-1830.
  • Paré G, et al. NEJM. 2010 Aug 29; online.
  • Rogan PK, et al. Pharmacogenetics. 2003;13(4):207‐18.
  • Shuldiner AR, et al. JAMA. 2009;302(8):849‐57.
  • Sibbing D, et al. Eur Heart J. 2009;30(8):916‐22.
  • Sibbing D, et al. Circulation. 2010;121(4):512‐8.
  • Sim SC, et al. Clin Pharmacol Ther. 2006;79(1):103‐13.
  • Simon T, et al. N Engl J Med. 2009;360(4):363‐75.
  • Tiroch KA, et al. Am Heart J. 2010 Sep;160(3):506‐12.
  • Trenk D, et al. J Am Coll Cardiol. 2008;51(20):1925‐34.
  • Varenhorst C, et al. Eur Heart J. 2009;30(14):1744‐52.
  • Wallentin L, et al. Lancet. 2010 Aug 27. [Epub ahead of print]

Test Methodology

Saliva samples were collected using Oragene DNA Collection Kits (DNA Genotek) and DNA was extracted manually according to the manufacturer’s instructions or automatically using a DNAdvance Kit (Agencourt). Purified DNA was quantified using UV absorbance at 260 nm. One microgram of the resulting DNA from each sample was used as template in the Affymetrix DMET Plus GeneChip assay. Data analysis was performed using Affymetrix DMET Console software.

To view your clinical report, click here. The clinical report contains the lab generated testing information and does not include all the content in the research study report.

[Risk interpretation based on Coriell's CYP2C19 Clopidogrel Metabolizer Type Genotype Translation Version 1 (March 2011)]

Coriell Institute for Medical Research
Coriell Genotyping and Microarray Center
403 Haddon Avenue Camden, NJ 08103
Phone: 856-966-7377 Fax: 856-964-0254  www.coriell.org
CYP2C19 Clinical Report
Name: NATALIE DEMO
Date of Birth:
Coriell ID: DEMONAT
Lab Accessioning Number: DEMONAT
Ordering Physician:
Sample Type: Saliva
Gender: Female
Date Collected:
Date Received:
Date of Report: 04/29/2011
NAME OF GENE: CYP2C19 LOCATION OF GENE: 10q24
Variants tested RESULT Reference Genotype
rs12248560 CC C C
rs28399504 GG A A
rs41291556 TT T T
rs72558184 GG G G
rs4986893 GG G G
rs4244285 GG G G
rs72558186 TT T T
rs56337013 CC C C
Risk interpretation based on Coriell's CYP2C19 Clopidogrel Metabolizer Type Genotype Translation Version 1 (March 2011)

Test Limitations

DNA-based testing is highly accurate, however there are many sources of potential error including: mis-identification of samples, rare technical errors, trace contamination of PCR reactions, and rare genetic variants that interfere with analysis. There may be other variants in the CYP2C19 gene, not included in this test, that influence metabolizer status. This test or one or more of its components was developed and its performance characteristics determined by the Coriell Institute for Medical Research. It has not been approved by the Food and Drug Administration (FDA). The FDA has determined that such approval is not necessary. The Coriell Institute is regulated under the Clinical Laboratory Improvement Amendments (CLIA) of 1988 as qualified to perform high-complexity testing.

Test Methodology

Saliva samples were collected using Oragene DNA Collection Kits (DNA Genotek) and DNA was extracted manually according to the manufacturer’s instructions or automatically using a DNAdvance Kit (Agencourt). Purified DNA was quantified using UV absorbance at 260 nm. One microgram of the resulting DNA from each sample was used as template in the Affymetrix DMET Plus GeneChip assay. Data analysis was performed using Affymetrix DMET Console software.

electronically signed by
Marie Hoover, PhD, Laboratory Director

Genetic Variant Definitions

  • Extensive metabolizers (EM) include those with two normally functioning copies such as CYP2C19*1.
  • Intermediate metabolizers (IM) include those with one normally functioning copy of CYP2C19 (CYP2C19*1) and one non-functional variant such as CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*6, CYP2C19*7 or CYP2C19*8.
  • Reduced Response - Metabolizer Status Uncertain includes those who have at least two non-functional variants in the CYP2C19 gene conferring a reduced response but for whom metabolizer status cannot be definitively determined to be poor or intermediate.
  • Poor metabolizers (PM) include those with two non-functional variants such as CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*6, CYP2C19*7 or CYP2C19*8.
  • Ultra rapid metabolizers (UM) include those with 2 enhanced activity variants such as CYP2C19*17 or one normally functioning copy (CYP2C19*1) and one enhanced activity variant (CYP2C19*17).
  • Typical or Increased Response – Metabolizer Status Uncertain includes those with zero non-functional variants, but for whom the presence of one or more enhanced activity variants cannot be determined due to technical limitations.
  • Metabolizer Status Uncertain includes those individuals for whom a metabolizer status cannot be assigned either due to technical limitations or due to the lack of clinical data on the effect of the variant combination.

References

  1. Mega JL, et al. N Engl J Med 2009; 360:354-62 PMID: 19106084
  2. Mega JL, et al. JAMA. 2010; 304; 1821-1830. PMID: 20978260
  3. Sibbing D, et al. J. Thromb. Haemost. 2010; 8:1685-1693. PMID:20492469
  4. Sibbing D, et al. Circulation. 2010; 121:512-518. PMID:20083681
  5. Simon T, et al. N Engl J Med 2009; 360(4):363-75. PMID: 19106083
  6. OMIM 124020 (http://www.ncbi.nlm.nih.gov/omim)
  7. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/
  8. http://www.cypalleles.ki.se/cyp2c19.htm