The Use of Genetics in Guiding Therapy

Human Leukocyte Antigens and Drug Hypersensitivity

June 2012

Drug hypersensitivity affects approximately 7% of the general population and can manifest as a variety of non-specific and oftentimes serious side-effects. Almost all drugs can induce hypersensitivity reactions which are typically dose-independent and unpredictable. Human leukocyte antigens (or HLA) play a central role in the immune reaction by initiating an immune response by presenting antigen to the T-cell receptor. The HLA genes are located at the major histocompatibility complex (MHC) region on chromosome 6 (6p21.3), which contains about 200 genes including more than 10 highly polymorphic HLA genes.

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Leukocyte Antigens and Drug Hypersensitivity

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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