1. How Genetic Variants Impact the Safety and Effectiveness of Drugs Pharmacogenetics © 2009 - 2014 PGXL Laboratories

2. Every human has a genetic code that is unique to them There is no perfect version of the code; we all have variants Variances in genes responsible for drug metabolism, transport and uptake/binding can: o Be of no consequence to the drug’s safety and efficacy o Render a medication useless o Result in a medication causing serious adverse reactions Pharmacogenetics The Study of How Our Genes Affect Our Response to Drugs

3. 1.There can be wide variability in patient response to commonly prescribed medications 2.Genetics is estimated to account for 20-95% of the variability in drug effects 3.Adverse Drug Reactions (ADRs) are the 6 th leading cause of death 4.A review of drugs most commonly associated with ADRs found that 57% (16 of 27) were metabolized by a gene with a known genetic polymorphism Pharmacogenetics Why It Matters

4. Pharmacogenetics Same Diagnosis, Same Medications, Different Outcomes No Variance Normal Response Variance Risk Decreased Variance Lack of Efficacy Variance High Risk Typical Clinic Day N=30

5. Incidence of Genetic Variants Important to Drug Selection and Drug Dose Gene % of Extensive Metabolizers % of Intermediate Metabolizers % of Poor Metabolizers % of Ultra-Rapid Metabolizers VARIANTS 2D653%35%10%2%47% 2C1936%32%4%28%64% 2C957%40%3%NA43% VKOR>70% 3A487%12%1%N/A13% 3A51%18%81%N/A99% SLC6A425%50%25%N/A75% 1. Pharmacogenetics Knowledge Base Implementation: www.pharmgkb.org Property of PGxl Laboratories

6. 1988 – International Human Genome Initiative (HGRI) launched 1989 – Dr. Roland Valdes launches post-PhD Molecular Clinical Chemistry program 1993 – Dr. Francis Collins assumes leadership of HGRI 1997 – Dr. Valdes and Dr. Mark Linder publish seminal pharmacogenetics paper Evolution of Pharmacogenetics PG XL Founders Are Pioneers in the Field Continued…

7. 2001 – PGXL Laboratories is first CLIA-certified pharmacogenetics specialist in U.S. 2004 – Human genome sequenced and published 2010 – Drs. Valdes and Linder publish guidelines for operating a pharmacogenetics laboratory Evolution of Pharmacogenetics PG XL Founders Are Pioneers in the Field …Continued

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