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.
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
CYP2C9/VKORC1/CYP4F2 WARFARIN GENE TEST
Name: STEVE CPMC
Date of Birth:
Coriell ID: DEMOSTEVE
Lab Accessioning Number: DEMOSTEVE
Ordering Physician:
Sample Type: Saliva
Gender: Male
Date Collected:
Date Received:
Date of Report: 06/11/2012
NAME OF GENE: CYP2C9 LOCATION OF GENE: 10q24
Variants tested RESULT Reference Genotype
rs1799853 (CYP2C9*2) CC C C
rs1057910 (CYP2C9*3) CC A A
rs28371686 (CYP2C9*5) CC C C
rs9332131 (CYP2C9*6) AA A A
rs28371685 (CYP2C9*11) CC C C
rs72558189 (CYP2C9*14) GG G G
^ When the Result for all CYP2C9 variants tested are the same as the reference, the Combined Result is called CYP2C9 *1/*1. In some cases, due to technical limitations, your Combined Result may be CYP2C9*Uncertain. 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).
NAME OF GENE: VKORC1 (-1639G>A) LOCATION OF GENE: 16p11.2
Variants tested RESULT Reference Genotype
rs9923231 AG G G
NAME OF GENE: CYP4F2 (433V>M) LOCATION OF GENE: 19p13
Variants tested RESULT Reference Genotype
rs2108622 GG G G
Risk interpretation based on Coriell's Warfarin Response Genotype Translation Version 1 (January 2012).

Interpretation

Based on this individual’s Combined Genetic Result: CYP2C9*1/*1, VKORC1-AG, CYP4F2-GG an Intermediate Dose1 of Warfarin MAY be Needed.

INR2 (clotting time) and clinical features should be used, in combination with genetic results, to establish warfarin dosing.

This interpretation is based on dosing guidance available in the FDA (Food and Drug Administration) drug label for warfarin (below). Dosing recommendations for individuals with CYP2C9 *5, *6, *11, and *14 are based on functional similarity to CYP2C9*2 (*11, *14), and *3 (*5, *6). CYP4F2 results have been incorporated into the interpretation based on dosing guidance from www.warfarindosing.org using two standard individuals age 50 and 75 with the following characteristics: female, diagnosis of atrial fibrillation, non smoker, BMI in the normal rang, no concomitant medications.


1 Intermediate therapeutic dose of 3-4mg/day based on FDA approved drug label for warfarin and Garcia et al 2005
2 INR - International Normalized Ratio is a measurement of clotting time
Range of Expected Therapeutic Warfarin Doses Based on CYP2C9 and VKORC1 Genotypes 1
VKORC1 CYP2C9
*1/*1 *1/*2 *1/*3 *2/*2 *2/*3 *3/*3
GG 5-7 mg 5-7 mg 3-4 mg 3-4 mg 3-4 mg 0.5-2 mg
AG 5-7 mg 3-4 mg 3-4 mg 3-4 mg 0.5-2 mg 0.5-2 mg
AA 3-4 mg 3-4 mg 0.5-2 mg 0.5-2 mg 0.5-2 mg 0.5-2 mg

1Ranges are derived from multiple published clinical studies. Other clinical factors (e.g., age, race, body weight, sex, concomitant medications, and comorbidities) are generally accounted for along with genotype in the ranges expressed in the Table. VKORC1 –1639 GA (rs9923231) variant is used in this table. Other co-inherited VKORC1 variants may also be important determinants of warfarin dose. Individuals with CYP2C9 *1/*3, *2/*2, *2/*3 and *3/*3 may require more prolonged time (>2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen.

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 CYP2C9 gene, VKORC1 gene or the CYP4F2 gene that are not included in this test, that influence the response to warfarin. 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

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