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: 01/11/2017

CYP2C19 and Voriconazole Response

These results were generated in a CLIA-approved laboratory as part of the Coriell Personalized Medicine Collaborative research study. Results take into account 10 genetic variants in the CYP2C19 gene, known to contribute to the metabolism of voriconazole. This report reflects this participant’s metabolism status predicted based on genetic testing but does not reflect whether they are currently taking voriconazole.

The CPMC has genetic counselors 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 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 voriconazole.

Your combination of genetic variant results is listed below in yellow.
Your CYP2C19* result is:

CYP2C19*4/*4
(Voriconazole Poor Metabolizer)

VARIANTS TESTEDYOUR RESULTREFERENCE VALUE
rs4244285 (CYP2C19*2) GG G G
rs4986893 (CYP2C19*3) GG G G
rs28399504 (CYP2C19*4) GG A A
rs56337013 (CYP2C19*5) CC C C
rs72558184 (CYP2C19*6) GG G G
rs72558186 (CYP2C19*7) TT T T
rs41291556 (CYP2C19*8) TT T T
rs17884712 (CYP2C19*9) GG G G
rs6413438 (CYP2C19*10) CC C C
rs12248560 (CYP2C19*17) CC C C
1When your variant result for all CYP2C19 variants tested are the same as the reference, the combined genetic result is called CYP2C19*1/*1. In some cases your combined genetic result may be uncertain. Other variants, not currently included in this CPMC test may influence this result and interpretation.

Interpretation of Your Results

Voriconazole Poor Metabolizer
CYP2C19 Result: CYP2C19*4/*4
  • Your combination of genetic variants indicates you are a voriconazole poor metabolizer with significantly decreased CYP2C19 activity.
  • Poor metabolizers process voriconazole at a very slow rate and may be at increased risk for adverse reactions (vision problems, rash, elevated liver enzymes) when taking a standard dose of voriconazole.
  • If prescribed voriconazole, talk to your doctor about appropriate monitoring or consider alternative treatment options.
  • 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.

How Common

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

Reduced CYP2C19 activity

Poor Metabolizer

3 out of 100 people

May be at increased risk for adverse reaction.
Voriconazole Poor Metabolizer Voriconazole Poor Metabolizer Voriconazole Poor Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer
Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer
Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer
Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Intermediate Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer
Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer
Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer
Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Extensive Metabolizer Voriconazole Ultra-Rapid Metabolizer
Voriconazole Ultra-Rapid Metabolizer Voriconazole Ultra-Rapid Metabolizer Voriconazole Ultra-Rapid Metabolizer Voriconazole Ultra-Rapid Metabolizer Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown
Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown
Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown Voriconazole Metabolizer Status Unknown

Intermediate Metabolizer

30 out of 100 people

May be at increased risk for adverse reaction.
Typical CYP2C19 activity

Extensive Metabolizer

36 out of 100 people

Expected to have a typical risk for adverse reaction.
Increased CYP2C19 activity

Ultra-Rapid Metabolizer

5 out of 100 people

Expected to have a typical risk for adverse reaction.
Uncertain CYP2C19 activity

Metabolizer Status Unknown

26 out of 100 people

Not enough data to determine risk for adverse reaction.

What is Voriconazole (Vfend®)?

Voriconazole is a medication used to treat serious fungal infections.

Uses:
  • Treatment of aspergillosis (a fungal infection in the lungs that can spread via bloodstream to other organs)
  • Treatment of esophageal candidiasis (a yeast infection that causes white patching in the mouth and throat)
  • Treatment of other yeast infections of the skin, stomach, kidney, bladder, and wounds
Risk Factors Affecting Response to Voriconazole

Genetic Risk Factors

Genetic variants, or changes, in a gene called CYP2C19 can affect the way your body metabolizes voriconazole. Some people with certain genetic variants may be at increased risk for side effects from taking a standard dose of voriconazole compared to people without these variants.

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 Voriconazole 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 Voriconazole 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 above.

Drug-Drug Interactions

In addition to your genes, how your body metabolizes voriconazole may prevent other medications that you take from working effectively and may increase the risk of side effects associated with these other medications.

The following medications, when taken with voriconazole, may reduce the benefit of taking the other medication or may increase the risk for side effects from the other medication:

MedicationAlso Known AsType
Carbamazepine Tegretol®, Carbatrol®, Equetro®, and Epitol® Anticonvulsant
Efavirenz, Ritonavir Sustiva® and Atripla®, Norvir® HIV Antiviral
Ergotamine/Dihydroergotamine Cafergot®, Ergomar® Migraine Pain
Phenobarbital Luminal® Long-acting barbituate
Pimozide Orap® Antipsychotic
Quinidine Quinaglute®, Quinidex® Antiarrhythmic
Rifabutin, Rifampin Mycobutin®, Rifadin® Antibiotic
Sirolimus Rapamune® Immunosuppressant

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

Other Interactions

In addition to your genes, and other medications, food and supplements may affect how your body responds to voriconazole (Vfend®) and may increase the risk of side effects when taking voriconazole (Vfend®).

The following foods, vitamins, and supplements are known to interact with voriconazole (Vfend®):


St. John’s Wort

  • St. John’s Wort is a medicinal herb that has antidepressant and anti-inflammatory properties.
  • Avoid taking St. John’s Wort while taking voriconazole (Vfend®).
  • Taking St. John’s Wort while taking voriconazole (Vfend®) reduces the amount of voriconazole available in the blood stream and may prevent voriconazole from working properly.

For a list of foods, vitamins, and supplements that may interact with voriconazole (Vfend®), 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 voriconazole.
  • Other factors such as body weight, various health conditions, and other medications may impact an individual’s response to voriconazole.
  • There may be other genetic variants within the CYP2C19 gene which influence response to voriconazole but are not included in this test.
  • There may be other genetic variants in the CYP2C19 gene for which response to voriconazole has not been documented and/or validated in multiple studies.
  • There may be genetic variants in other genes that influence response to voriconazole.
  • This result reflects published data available at the time this gene-drug pair was approved by the CPMC Informed Cohort Oversight Board (November 2016). 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, we will be unable to interpret one or more gene variants. In this case you will not receive a result for those variants and in some cases your drug response cannot be interpreted. 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.
  • In some cases, the CYP2C19 metabolizer status on your voriconazole report will be different than the CYP2C19 metabolizer status on your Clopidogrel (Plavix®) report. For an explanation of why your CYP2C19 metabolizer status may be different for different drugs, click here.

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
  • Ikeda Y, et al. Clin Pharmacol Ther. 2004 Jun;75(6):587-8.
  • Karlsson MO, et al. Antimicrob Agents Chemother. 2009 Mar;53(3):935-44.
  • Lei, HP, et al. Ann Pharmacother 43(4): 726-731.
  • Levin, MD, et al. J Antimicrob Chemother 60(5): 1104-1107.
  • Matsumoto K, et al. Int J Antimicrob Agents. 2009 Jul;34(1):91-4.
  • Mikus G, et al. Clin Pharmacol Ther. 2006 Aug;80(2):126-35.
  • Rengelshausen, JM, et al. Clin Pharmacol Ther 78(1): 25-33.
  • Wang G, et al. Eur J Clin Pharmacol. 2009 Mar;65(3):281-5.
  • Weiss J, et al. J Clin Pharmacol. 2009 Feb;49(2):196-204.

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/Voriconazole Response Genotype Translation Version 1 (January 2017)]

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 GENE TEST FOR VORICONAZOLE RESPONSE
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: 01/11/2017
NAME OF GENE: CYP2C19 LOCATION OF GENE: 10q24
Variants tested RESULT Reference Genotype
rs4244285 (CYP2C19*2) GG G G
rs4986893 (CYP2C19*3) GG G G
rs28399504 (CYP2C19*4) GG A A
rs56337013 (CYP2C19*5) CC C C
rs72558184 (CYP2C19*6) GG G G
rs72558186 (CYP2C19*7) TT T T
rs41291556 (CYP2C19*8) TT T T
rs17884712 (CYP2C19*9) GG G G
rs6413438 (CYP2C19*10) CC C C
rs12248560 (CYP2C19*17) CC C C
^ When the Result for all CYP2C19 variants tested are the same as the reference, the Combined Result is called CYP2C19 *1/*1. In some cases, due to technical limitations, your Combined Result may not be able to be determined. It may still be possible to provide an interpretation for such a result based on possible genetic outcomes (for example in rare combinations of non-reference results at more than one variant, or the presence of a “result not available” at one or more variants).
Risk interpretation based on Coriell’s CYP2C19/Voriconazole Response Genotype Translation Version 1 (January 2017).

Interpretation

This individual is expected to be a Voriconazole Poor Metabolizer based on the Combined Genetic Result: CYP2C19*4/*4

Individuals who are poor metabolizers eliminate voriconazole more slowly and may be at increased risk for adverse reactions when taking a standard dose of voriconazole.

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 that are not included in this test, that influence the response to voriconazole. 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
Owatha L. Tatum, PhD, Laboratory Director


References

  1. Ikeda Y, et al. Clin Pharmacol Ther. 2004 Jun;75(6):587-8.
  2. Karlsson MO, et al. Antimicrob Agents Chemother. 2009 Mar;53(3):935-44.
  3. Lei, HP, et al. Ann Pharmacother 43(4): 726-731.
  4. Levin, MD, et al. J Antimicrob Chemother 60(5): 1104-1107.
  5. Matsumoto K, et al. Int J Antimicrob Agents. 2009 Jul;34(1):91-4.
  6. Mikus G, et al. Clin Pharmacol Ther. 2006 Aug;80(2):126-35.
  7. Rengelshausen, JM, et al. Clin Pharmacol Ther 78(1): 25-33.
  8. Wang G, et al. Eur J Clin Pharmacol. 2009 Mar;65(3):281-5.
  9. Weiss J, et al. J Clin Pharmacol. 2009 Feb;49(2):196-204.