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Name:
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NATALIE DEMO
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Date of Birth:
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Coriell ID:
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DEMONAT
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Lab Accessioning Number:
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DEMONAT
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Ordering Physician:
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Gender:
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Female
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Date Collected:
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Date Received:
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Date of Report:
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06/11/2012
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CYP2C9, VKORC1, CYP4F2 and Warfarin (Coumadin®) Response
These results were generated in a CLIA-approved laboratory as part of the Coriell
Personalized Medicine Collaborative research study. Results take into account 6
genetic variants in the CYP2C9 gene, one genetic variant in the VKORC1 gene, and
one genetic variant in the CYP4F2 gene. Variation in these three genes is known
to influence the dose of warfarin needed to prevent blood clots without causing
dangerous side effects. This report reflects this participant’s predicted dosing
category (low, intermediate, high) based on their genetic results but does not reflect
whether they are currently taking warfarin. In addition, predicted dosing category
does not account for other factors known to influence dosing including age, weight,
gender, race, diet, other medications and smoking status.
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 combination of genetic variant results (listed below in yellow) indicates:
Increased Dose1 of Warfarin MAY be Needed
VARIANTS TESTED
(also known as) | REFERENCE VALUE | YOUR RESULT | YOUR COMBINED GENETIC RESULT2 |
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rs1799853 (CYP2C9*2)
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C C
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CC
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rs1057910 (CYP2C9*3)
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A A
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AA
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rs28371686 (CYP2C9*5)
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C C
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CC
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rs9332131 (CYP2C9*6)
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A A
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AA
| CYP2C9*1/*1 |
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rs28371685 (CYP2C9*11)
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C C
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CC
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rs72558189 (CYP2C9*14)
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G G
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GG
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rs9923231
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G G
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GG
| VKORC1-GG |
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rs2108622
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G G
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GG
| CYP4F2-GG |
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1
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Please see the Your Result Interpretation tab for the impact of this result on warfarin
dosing and risks.
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2
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Your personal combination of Variant Results is used to determine your Combined
Genetic Result. When your Variant Result for all CYP2C9 variants tested are the
same as the reference, the Combined Genetic Result is called CYP2C9 *1. In some
cases your Combined Genetic Result may be uncertain.
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Other variants, not currently included in this CPMC test may influence this result
and interpretation.
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Your combination of genetic results indicates that you may not respond adequately to an intermediate1 therapeutic dose of warfarin.
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If you require treatment with warfarin, a higher than intermediate1 therapeutic dose may be needed.
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You may be at an increased risk for blood clots if prescribed warfarin using intermediate dosing guidelines.
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INR2 (clotting time) and clinical features should be used, in combination with your genetic results, to establish warfarin dosing.
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This result may also affect your response to other medications. For more information on other medications that are affected by variants in the CYP2C9, VKORC1 and CYP4F2 genes, click here.
1 Based on an intermediate therapeutic dose of 3-4mg/day
2 INR - International Normalized Ratio is a measurement of clotting time
Increased Dose Indicated
88
out of 100 people
An increased dose may be needed to reach the full effect of warfarin. Increased
risk for blood clot at an intermediate dose.
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Intermediate Dose Indicated
12
out of 100 people
Expected to benefit from the intermediate dose.
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Lower Dose Indicated
0
out of 100 people
A lower dose of warfarin may be needed. Increased risk for excessive bleeding at
an intermediate dose.
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1
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FDA drug label dosing guidelines are based CYP2C9 and VKORC1 genotypes and an intermediate
therapeutic daily doses of 3-4mg/day.
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Genetic Risk Factors
Genetic variants, or changes, in three genes called CYP2C9, VKORC1, and CYP4F2 can
affect the way your body responds to warfarin.
Some people with certain genetic variants may require a higher or lower dose of
warfarin compared to people without these variants.
Non-Genetic Risk Factors
Many factors affect how your body responds to medications.
Non-genetic factors that may influence your response to warfarin include: diet,
lifestyle, medical history and interactions between medications.
Genes Affecting Warfarin Response:
CYP2C9, VKORC1, CYP4F2
For information on how CYP2C9, VKORC1 and CYP4F2 affect how the body responds to
warfarin click here.
Types of Results
Some genes (CYP2C9) have multiple variants. When a gene has multiple variants a
number system is used to name common combinations of variants (example: CYP2C9*2).
Some variant combinations have not been assigned a number yet. Other combinations
of variants cannot be assigned a number with certainty. Other genes including VKORC1
and CYP4F2 have only one variant that is known to affect the gene function (example:
Variant = A, Reference/Normal = G). Because there are multiple genes involved in
how your body responds to warfarin you will receive multiple results.
Your personal result and interpretation can be found
by clicking on the RESULTS tab above.
There are over 100 medications that, when taken with warfarin,
can cause an increase in the effect of warfarin and may result in increased
risk for bleeding.
There are over 40 medications that, when taken with warfarin, can
cause a decrease in the effect of warfarin and may result in an increased risk
for blood clots.
For a list of medications that may affect your response
to warfarin, click here.
To check for interactions between warfarin and medications you may be taking, click here.
The following Foods, Vitamins and Supplements are known
to interact with warfarin:
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Agrimony
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Alfalfa
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Aloe Gel
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Angelica (Dong Quai)
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Aniseed
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Arnica
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Asafoetida
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Aspen
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Black Cohosh
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Black Haw
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Bladder Wrack (Fucus)
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Bogbean
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Boldo
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Bromelains
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Buchu
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Capsicum
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Cassia
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Celery
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Chamomile (German and Roman)
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Clove
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Coenzyme Q10
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Cranberry
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Dandelion
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Danshen
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Fenugreek
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Feverfew
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Garlic
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German Sarsaparilla
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Ginger
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Ginkgo Biloba
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Ginseng (Panax)
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Goldenseal
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Horse Chestnut
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Horseradish
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Inositol Nicotinate
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Licorice
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Meadowsweet
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Mistletoe
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Nettle
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Onion
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Parsley
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Passion Flower
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Pau d’arco
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Policosanol
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Poplar
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Prickly Ash (Northern)
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Quassia
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Red Clover
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Senega
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St. John's wort
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Sweet Clover
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Sweet Woodruff
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Tamarind
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Tonka Beans
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Wild Carrot
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Wild Lettuce
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Willow
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Wintergreen
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Yarrow
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For a list of list of foods, vitamins and supplements that may
affect your response to warfarin, 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 warfarin.
- Other factors such as body weight, various health conditions, and other medications
may impact an individual’s response to warfarin.
- There may be other genetic variants within the CYP2C9 gene, VKORC1 gene or CYP4F2
gene which influence response to warfarin but are not included in this test.
- There may be other genetic variants for which response to warfarin has not been
documented and/or validated in multiple studies.
- There may be genetic variants in other genes that influence response to warfarin.
- This result reflects published data available at the time this gene-drug pair result
was prepared (December 2011). 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. 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
- Caldwell MD, et al. Blood. 2008;111(8):4106-12.
- Pérez-Andreu V, et al. Blood. 2009;113(20):4977-9.
- Wadelius M, et al. Pharmacogenomics J. 2005;5(4):262-70.
- Wadelius M, et al. Blood. 2009;113(4):784-92.
- Lindh JD, et al. Clin Pharmacol Ther. 2005;78(5):540-50.
- Sanderson S, et al. Genet Med. 2005;7(2):97-104.
- Dickmann LJ, et al. Mol Pharmacol. 2001;60(2):382-7.
- Cavallari LH, et al. Clin Pharmacol Ther. 2010; 87(4):459-64.
- Ieiri I, et al. Ther Drug Monit. 2000; 22:237-44.
- Zhao F, et al. Clin Pharmacol Ther. 2004; 76:210-9.
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 Warfarin Response Genotype Translation Version 1 (January 2012)]
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