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Name:
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STEVE CPMC
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Date of Birth:
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Coriell ID:
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DEMOSTEVE
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Lab Accessioning Number:
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DEMOSTEVE
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Ordering Physician:
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Gender:
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Male
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Date Collected:
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Date Received:
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Date of Report:
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02/07/2013
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TPMT and Thiopurine Response
These results were generated in a CLIA-approved laboratory as part of the Coriell
Personalized Medicine Collaborative research study. Results take into account 4
common genetic variants in the TPMT gene. Variants in the TPMT gene are known to
affect the metabolism of thiopurine drugs such as azathioprine (Imuran®), mercaptopurine
(Purinethol®), thioguanine (6-TG, Tabloid® or Lanvis®). People with certain genetic
variants may require a lower dose or may be at risk for severe, life threatening,
side-effects including bone marrow suppression. This report reflects the participant’s
predicted TPMT activity level (low/absent, intermediate/reduced, or typical) based
on their genetic results but does not reflect whether or not they are currently
taking a thiopurine drug. In addition, predicted TPMT activity level does not account
for other factors that may influence dosing including age, weight, gender, race,
diet and other medications.
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 combination of genetic variant results is listed below in yellow. Your TPMT
* result is
TPMT*3A/*3C
(TPMT Low/Absent Activity)
| VARIANTS TESTED | YOUR RESULT | REFERENCE VALUE |
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rs1142345 (TPMT*3C)
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GG
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A A
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rs1800584 (TPMT*4)
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GG
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G G
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rs1800460 (TPMT*3B)
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AG
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G G
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rs1800462 (TPMT*2)
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GG
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G G
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1When your variant result for all TPMT variants tested are the same as
the reference, the combined genetic result is called TPMT *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.
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Your combination of genetic variants is associated with low or absent TPMT activity.
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People with low/absent TPMT activity are at an increased risk of developing severe, life-threatening bone marrow suppression when taking a standard dose of a thiopurine drug. Bone marrow suppression is a severe decrease in cells responsible for providing immunity, carrying oxygen, and those responsible for normal blood clotting.
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If you need an immune suppressant, talk to your doctor about treatment options other than thiopurine drugs.
TPMT Low/Absent Activity
0
out of 100 people
Thiopurine drugs may be toxic. Increased risk of developing severe, life threatening
side effects (bone marrow suppression) if prescribed a standard dose.
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TPMT Intermediate (Reduced) Activity
6
out of 100 people
May be at an increased risk for toxicity at a standard dose of a thiopurine drug.
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TPMT Typical Activity
94
out of 100 people
Expected to respond to a standard dose of a thiopurine drug. No increased risk of
side effects due to gene status.
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Genetic Risk Factors
Genetic variants, or changes, in a gene called TPMT can affect the way your body
processes thiopurine drugs.
Some people with certain genetic variants may require a lower dose or may be at
risk for severe, life threatening, side-effects including bone marrow suppression,
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.
Genes Affecting Thiopurine Activity:
TPMT
Types of Results
There are four common variants in the TPMT gene that are known to affect the gene
function. A number system has been created to name combinations of these variants.
We all have 2 copies of every gene; when possible, you will have a TPMT result with
two numbers.
Example: TPMT *1/*2
Your personal result and interpretation can be found
by clicking on the RESULTS tab
above.
The following medications, when taken with a thiopurine drug, may increase the risk for
side effects:
| Medication | Also Known As |
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Allopurinol
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Lopurin, Zyloprim
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Warfarin
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Coumadin, Jantoven
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ACE inhibitors
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Lotensin, Capoten, Vasotec
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Ribavirin
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Copegus, Rebetol, RibaTab, RibaSphere
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Aminosalicylates
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Colazal, Asacol, Dipentum, Azulfidine
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For a selected list of other medications that can also affect your response to:
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 response to thiopurine drugs.
- Other factors such as body weight, various health conditions, and other medications
may impact an individual’s response to thiopurine drugs.
- There may be other genetic variants within the TPMT gene which influence response
to thiopurine drugs but are not included in this test.
- There may be other genetic variants in the TPMT gene for which response to thiopurine drugs
has not been documented and/or validated in multiple studies.
- There may be genetic variants in other genes that influence response to thiopurine drugs.
- This result reflects published data available at the time this gene-drug pair was
approved by the CPMC Informed Cohort Oversight Board (December 2010). 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).
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
- Ansari A, et al. Aliment Pharmacol Ther. 2008; 28(8): 973-83.
- Ansari A, et al. Aliment Pharmacol Ther. 2002; 16(10): 1743-50.
- Anstey A V, et al. Br J Dermatol. 2004; 151(6): 1123-32.
- Black A J, et al. Ann Intern Med. 1998; 129(9): 716-8.
- Dong X W, et al. World J Gastroenterol. 2010; 16(25): 3187-95.
- Higgs J E, et al. Pharmacogenomics. 2010; 11(2): 177-88.
- Kaskas BA, et al. Gut. 2003; 52(1): 140-2.
- Lennard L, et al. Lancet 1990; 336(8709): 225-9.
- Oselin K and Anier K. Drug Metab Dispos. 2007; 35(9): 1452-4.
- Sanderson J, et al. Ann Clin Biochem 2004; 41(Pt 4): 294-302.
- Weinshilboum R M. and Sladek SL. Am J Hum Genet 1980; 32(5): 651-62.
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 TPMT Activity Genotype Translation Version 1 (December 2010)]
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