Iowa Institute of Human Genetics

  • IIHG Drug Metabolism Test

    About this test

    A key area of clinical importance in the field of human genetics is that of gene-drug interactions, commonly called Pharmacogenomics (PGx). Several gene-drug pairs affecting drug metabolism and transport have been identified. The most well-studied and validated of these genes are the Cytochrome P450 (CYP) enzymes, which have a role in the metabolism of a large number of drugs. Identifying a patient’s DNA profile for these genes can help determine which drugs at what dose are the most effective and cause the fewest side-effects.  

    The Iowa Institute of Human Genetics (IIHG) offers an integrated drug metabolism (pharmacogenomic) test for clopidogrel (Plavix®) and opioid medications. The IIHG drug metabolism test can be ordered preemptively by a physician as a tool in the health care management of their patients.

    We have developed a custom multi-gene panel test and analysis pipeline in collaboration with the University of Iowa Hospitals and Clinics Department of Pharmaceutical Care, and University of Iowa College of Pharmacy. The multidisciplinary IIHG-UIHC Pharmacogenomics Team reviews all results, and the ordering physician receives a report of clinically relevant results for each patient. Result reports have been developed in collaboration with UIHC physicians and pharmacists and educational materials are incorporated into the report to aid health care providers in the interpretation of results. The IIHG can provide education materials and assistance to the health care provider so he/she may counsel the patient with confidence.

    Did you know?

    •  Drugs do not work well in half of people who take them.
    • The FDA currently suggests genetic testing for 10% of all drugs.

    Indications for Testing

    Opioid Metabolism (CYP2D6 gene):

    The IIHG Drug Metabolism Test analyzes gene variants to allow you to determine prior to surgery if your patient has variants in the CYP2D6 gene that cause them to have altered opioid metabolism.

    The CYP2D6 gene regulates the metabolism of codeine, and tramadol (Ultram®) for pain relief. The test looks at DNA changes (variants) in CYP2D6 that can alter the metabolism of opioids. Knowing the type of CYP2D6 gene your patient has can help you decide which pain medicine will work best for your patient.

    Common indications for testing include:

    • Patients who will have surgery in the future.
    • Patients who experience insufficient pain relief.

     The CYP2D6 gene can also regulate the metabolism of some antidepressants, like tricyclics, and Tetrabenzine (Xenazine). Please contact the IIHG-UIHC Pharmacogenomics Stewardship Program if you have questions about the use of the results of this test for other medications.

    Clopidogrel (Plavix®) (CYP2C19 gene)

    Did you know 30% of patients cannot metabolize clopidogrel due to their DNA variants? 

    The IIHG Drug Metabolism Test analyzes gene variants to allow you to determine if your patient has variants in the CYP2C19 gene that prevent them from metabolizing Clopidgrel.

    Common indications for testing include:

    • Patients at elevated risk for stroke; or
    • Patient with unstable angina; or
    • Patient with non-ST-elevation myocardial infarction; or
    • Patient who experiences recurrent acute coronary syndromes (unstable angina/myocardial infarction) despite ongoing therapy with clopidogrel.

    *Source: Wellmark Inc. 2015

    How to order the test

    This is a send out test. To order the test, please complete the following forms which are available on our website:

    • Drug Metabolism Requisition Form  
    •  UIHC health care providers should place a test order as a Miscellaneous test in EPIC - titled Drug Metabolism Testing.
    • Health care providers outside of the University of Iowa Hospitals and Clinics may order the test by mailing the completed requisition form and sample to the address listed below. 
    • This test must be ordered by a health care provider. Patients are not permitted to order the test for themselves.

    Specimen Type 

    * All samples must be labeled with the patient's name, date of birth, and date of collection.

    • 6 mL whole blood in lavender EDTA tube (3 mL pediatric minimum). Samples must be received within 72 hours of sample collection.
    • 10 µg DNA (A260/A280 1.8-2) resuspended in 0.1mM EDTA (10mM Tris HCl, 0.1mM EDTA, pH 8, Teknova Cat# T0220)

    After collection, samples should be stored and shipped at room temperature.

    Please note: Specimens for which insufficient quality or quantity of DNA is obtained, an additional sample will be requested. Incorrect handling or shipping of specimens can result in insufficient quality or quantity of DNA.

    Shipping Requirements

    • After collection, samples should be stored and shipped at room temperature.
    • Delivery: will receive Monday-Friday

    Iowa Institute of Human Genetics
    University of Iowa
    285 Newton Road, 5296 CBRB
    Iowa City, IA 52242
    Phone: 319-335-3688

    Cost

    • Your institution will be billed $499 for this test.
    • Insurance may not cover this test.
    • This test corresponds with CPT Codes 81225, 81226.
    • This test is covered for UIChoice insurance holders.
    • Medicare will cover up to 80% of the cost of this test.  

    Billing

    • At this time the IIHG only accepts Institutional Billing.
    • We do not bill patients directly.
    • We cannot accept credit card payments at this time.

    *Please note: billing information MUST be complete before samples will be processed.

    Turnaround Time

     Approximately 6 weeks after receipt at the IIHG lab.

    • Weeks 1 and 2: Sample collection and processing
    • Week 3: Library preparation and sequencing
    • Week 4: Data analaysis
    • Weeks 5 and 6: Results confirmation
    • Week 7: Team sign out of results and generation

    Results Reporting  

    • Result reports will be faxed to the referring physician(s) indicated on the test requisition.

    Methodology 

    • Targeted sequence capture followed by massively parallel sequencing using the IIHG PGx xGen® Lockdown® Probes and the Illumina MiSeq sequencer to detect DNA variations in CYP2C19 and CYP2D6.
    • A custom in-house informatics analysis pipeline has been developed to translate DNA variants to a patient's drug metabolizer status.
    • Only variants with a known metabolizer status and clinical recommendations are reported. Novel variants are not analyzed or reported.
    • Data sensitivity and specificity for testing is >99.9%. Pharmacogenomic DNA variants are covered at our depth-of-coverage minimum threshold (30 reads). In general, >99% of single nucleotide variant calls and small insertion/deletion variant calls are confirmed when compared to an orthogonal technology.
    • Reported single nucleotide variants and the copy number variant CYP2D6 *5 are confirmed by an orthogonal technology (such as Sanger Sequencing or TaqMan Assay).

    Interpretation of Results 

    • IIHG Pharmacogenomic Team reviews the results. The team includes physicians, scientists, bioinformaticians, pharmacists, and genetic counselors.
    • Variants are classified and clinical recommendations are made in accordance to the CPIC: Clinical Pharmacogenetics Implementation Consortium.
    • Note: At this time, the IIHG provides results for CYP2D6 variants affecting response to opioids including codeine and tramadol and CYP2C19 variants affecting clopidogrel response. Variants in these two genes also affect the metabolism of other drugs.

    Technical Limitations 

    • It is not known how all medications are metabolized.
    • This is a targeted capture sequence test, therefore, variants in genes not included on this panel will not be found.
    • This assay is designed to amplify specific allelic variants of CYP2C19 and CYP2D6. Mutations in other areas of CYP2C19 and CYP2D6 are not detectable with this assay. Only variants with clinical recommendations are analyzed and reported. Based on our analysis pipeline we will not find variants that do not have clinical recommendations. (CPIC)
    • Please note, it is important to understand the absence of a reportable variant in a given gene does not mean there are not pathogenic variants in that gene.
    • The variant causing the patient's altered drug metabolism may not be detected because: some types of variants are very difficult to identify; and it may not be included in the sequenced/studied region. Typically, single nucleotide variations, and small insertions or deletions (indels) can be detected.
    • The test cannot predict drug metabolism severity.
    • If a variant is identified, it may not be recognized as drug metabolism altering because the understanding of the genome is not complete and it is not possible to predict with 100% accuracy the effect of all variants.
    • Interpretation of results is based on the current understanding of the human genome and human health and disease. The test may detect variants of uncertain clinical significance. Efforts will be made to limit these types of results.

    Resources and Education

    •  The IIHG-UIHC Pharmacogenomics Stewardship Program includes physicians, pharmacists, and a genetic counselor who can answer any questions you have regarding metabolism of other medications may be altered based on your patients results.  
    •  The IIHG Pharmacogenomic team can assist you with the following:
      • Understanding the result report and interpretation
      • Answer any questions regarding the IIHG Drug Metabolism test
       

    Phone: 319-335-3688
    Pager: 1576
    Email: iihg@uiowa.edu

    • To learn more about drug metabolism, please check back soon for health care provider education resources, including upcoming courses, seminars, or grand rounds presentations.
    • If you would like to schedule an educational event for your department, please contact the IIHG at 319-335-3688 or iihg@uiowa.edu.
    • To request patient education brochures for your clinic please contact us at iihg@uiowa.edu.

    Future Test Updates 

    • Please let us know if there is a medication you would like the IIHG to include on future versions of this test.
    • We are working on integrating the results of this test into MyChart and patient visit summary reports.

    Helpful Websites

    Clinical Pharmacogenetics Implementation Consortium (CPIC) 

    Peer-reviewed clinical guidelines published by PharmGKB and the Pharmacogenomics Research Network

    www.pharmgkb.org/page/cpic

    Genetics Home Reference

    Information about how genes affect your health: what genes are, how they work, and how they can cause illnesses

    www.ghr.nlm.nih.gov 

    The Pharmacogenomics Knowledgebase

    Information about how genes interact with medication

    www.pharmgkb.org 

    Contact Information
    Iowa Institute of Human Genetics
    University of Iowa 
    285 Newton Road, 5296 CBRB
    Iowa City, IA, 52242
    Telephone: 319-335-3688
    Fax: 319-335-3484 
    Email: iihg@uiowa.edu
    www.medicine.uiowa.edu/humangenetics

    About Pharmacogenomic Testing at Iowa (Audio)

    Courtesy of mendelspod.com