The Use of Genetics in Guiding Therapy

Warfarin PGx

June 2012

There are two major genes involved in warfarin PGx. CYP2C9 is one of the enzymes responsible for the metabolism of warfarin. Two common star alleles in the CYP2C9 gene, known as *2 and *3, lead to decreased enzymatic activity and warfarin sensitivity. The second gene is VKORC1, which encodes for the vitamin K epoxide reductase complex, subunit 1. A common promoter variant at -1639G>A, can lead to warfarin sensitivity or mild warfarin resistance, depending on which combination of alleles are present. The table show here is from the warfarin, or Coumadin, package insert. This table is a genotype-guided dosing table and is based on the combination of CYP2C9 *2 and *3 alleles and VKORC1 promoter polymorphism alleles that may be present in an individual.

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Warfarin PGx

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• Introduction
• Pharmacogenomics
• PGx Biomarkers in Drug Labels
• FDA-Approved Drugs with PGx-Related Label Information
• FDA-Approved Drugs with PGx-Related Label Information
• The FDA and PGx-Related Drug Label Updates
• Clopidogrel (Plavix)
• CYP2C19 and Response to Clopidogrel
• CYP2C19 and Response to Clopidogrel (cont)
• CYP2C19 PGx Testing for Clopidogrel
• Mayo CYP2C19 Test
• The FDA and PGx-Related Drug Label Updates
• Warfarin
• Warfarin PGx
• Allele Frequencies
• Medco-Mayo Warfarin Effectiveness Study
• Mayo Test for Warfarin Sensitivity
• FDA-Approved Drugs with PGx-Related Label Information
• Most Psychotropic Medications Are Metabolized by CYPs
• CYP450 Testing — Psychotherapeutics
• CYP2D6
• Mayo Test for CYP2D6
• Mayo Tests for CYP2D6
• Additional Mayo Tests for Psychiatric Applications
• The FDA and PGx-Related Drug Label Updates
• UGT1A1
• Irinotecan Metabolism
• UGT1A1 Genetic Variants
• Mayo Tests for UGT1A1
• The FDA and PGx-Related Drug Label Updates
• Human Leukocyte Antigens and Drug Hypersensitivity
• HLA-B*1502
• Mayo Test for HLA-B*1502
• HLA-B*5701
• Mayo Test for HLA-B*5701
• Summary
• Questions