PRODUCED BY PharmaQx report for JOHN SMITH Take charge of your health THE OBJECTIVES OF PHARMAQX The PharmaQx pharmacogenetic analysis useful for : 1. determining whether you are at risk of experiencing side effects following the administration of a medication; 2. determining which medications are likely to be inefficient for you; 3. provide your healthcare professional recommendations regarding the dosage and use of medications. According to your genetic profile, a notification is provided for each medication, highlighting which medications are likely to cause side effects or be inefficient. This report is provided for information purposes only and cannot be considered as a diagnostic tool. WHAT IS ANALYZED? PharmaQx identifies the presence of genetic variations in six (6) genes. In turn, these genes determine how to build six (6) enzymes implicated in the response to the twenty-five (25) medications included in this test. By identifying these genetic variations, we can predict whether the resulting enzyme will be functional or not. Each enzyme is then categorized in terms of is level of activity, which can go from non-fonctional to ultra-rapid. PharmaQx offers its products and services in order to better inform healthcare professionals on the genetic backgound of its clients and the link between genetics and drug response. Do not change current and/or future therapies without first consulting your doctor. © BIOGENIQ INC. 1 DOES PHARMAQX PROVIDE INFORMATION ABOUT MY SUSCEPTIBILITY FOR DISEASES OR CONDITIONS? No. None of the genetic variations analyzed by PharmaQx have been convincingly associated with a disease or condition. WHAT TYPE OF ANALYSIS IS DONE? Your DNA is extracted from the saliva sample you provided. Then, we determine the presence of genetic variations using a technique called genotyping. Unlike DNA sequencing, which consists of "reading" each DNA unit (nucleotide) one after the other, genotyping only analyzes specific positions that are of interest to us. In other words, PharmaQx only offers information regarding the response to medication. WHAT ARE THE LIMITS OF PHARMAQX? Despite the fact that our tests are more than 99% accurate, there is always a small probability that an error may occur. The genetic variations analyzed by PharmaQx are known by the scientific community. It is possible that an individual carries a new variation, that has not yet been identified as being implicated in the response to medication. In this case, the PharmaQx analysis will not detect this rare variation and the individual could receive an inappropriate recommendation. It is also possible that other genes are also implicated in the response to medication but that are not included in PharmaQx. PharmaQx offers its products and services in order to better inform healthcare professionals on the genetic backgound of its clients and the link between genetics and drug response. Do not change current and/or future therapies without first consulting your doctor. © BIOGENIQ INC. 2 TABLE OF CONTENTS Intoduction ..........................1 ANALGESIA Genetic summary ....................4 Codeine ......................33 Pharmacogenetic summary . 5 Oxycodone ....................35 Tramadol .....................37 CANCER, IMMUNOLOGY AND INFLAMMATION PSYCHIATRY Azathioprine ...................9 Amitriptyline ..................39 Mercaptopurine ................11 Aripiprazole ..................41 Tamoxifen ....................13 Atomoxetine .................. 43 Thioguanine . ..................15 Clomipramine .................45 CARDIOLOGY Desipramine ..................47 Clopidogrel ...................17 Doxepin .......................49 Flecainide ....................19 Haloperidol ...................51 Metoprolol ....................21 Imipramine ...................53 Simvastatin ...................23 Nortriptyline ..................55 Warfarin ......................25 Trimipramine .................57 GASTROENTEROLOGY Esomeprazole .................27 Glossary ...........................59 Lansoprazole .................29 Omeprazole ..................31 PharmaQx offers its products and services in order to better inform healthcare professionals on the genetic backgound of its clients and the link between genetics and drug response. Do not change current and/or future therapies without first consulting your doctor. © BIOGENIQ INC. 3 GENETIC SUMMARY JOHN SMITH Sex M Date of report 2014-12-17 Ethnicity Caucasian Type of specimen Saliva Birthdate 1952-10-15 Sample number BIO-001-00001 A total of six (6) genes were analyzed to generate your PharmaQx report (see table below). In general, you carry two versions of each gene, called alleles. By taking into consideration the individual activity of each one of your alleles, we deteremined your resulting enzymatic activity. Of note: according the scientific nomenclature, each gene and its associated enzyme share the same name (ex : CYP2C9). GENE ALLELES PHENOTYPE Name given to the Versions Resulting enzymatic activity DNA sequence of your gene (based on all of your alleles) CYP2C9 *1/*1 extensive metabolizer (normal function) CYP2C19 *1/*2 intermediate metabolizer (reduced function) CYP2D6 *2A/*2A extensive metabolizer (normal function) TPMT *3B/*3C poor activity (non-functional) VKORC1 *1/*3 high activity (increased function) SLCO1B1 *1A/*1A extensive activity (normal function) The genes analyzed for PharmaQx are presented in the table above. You have two copies of each gene (your alleles). The resulting enzymatic activity is indicated under the phenotype column (phenotype), APPROVED BY: _______________________________________ DATE:____________________ PharmaQx offers its products and services in order to better inform healthcare professionals on the genetic backgound of its clients and the link between genetics and drug response. Do not change current and/or future therapies without first consulting your doctor. © BIOGENIQ INC. 4 Date of report 2014-12-17 Sample number BIO-001-00001 PHARMACOGENETIC SUMMARY Now that your genes have been analyzed and that we determined your resulting enzymatic activity, we identified the medications that should be used with caution. CAUTION IS ADVISED FOR THE FOLLOWING MEDICATIONS MEDICATION ENZYME : PHENOTYPE NOTIFICATION CANCER, IMMUNOLOGY AND INFLAMMATION AZATHIOPRINE TPMT : Increased risk of side effects with p.9 poor activity conventional dosing of azathioprine. MERCAPTOPURINE TPMT : Increased risk of side effects with p.11 poor activity conventional dosing of mercaptopurine. THIOGUANINE TPMT : Increased risk of side effects with p.15 poor activity conventional dosing of thioguanine. CARDIOLOGY CLOPIDOGREL CYP2C19 : Increased probability of treatment failure p.17 intermediate metabolizer with conventional dosing of clopidogrel. PharmaQx offers its products and services in order to better inform healthcare professionals on the genetic backgound of its clients and the link between genetics and drug response. Do not change current and/or future therapies without first consulting your doctor. © BIOGENIQ INC. 5 Date of report 2014-12-17 Sample number BIO-001-00001 NO WARNING FOR THE FOLLOWING MEDICATIONS MEDICATION ENZYME : PHENOTYPE NOTIFICATION CANCER, IMMUNOLOGY AND INFLAMMATION TAMOXIFEN CYP2D6 : No genetic variations were identified that p.13 extensive metabolizer would prompt changes in therapy. CARDIOLOGY FLECAINIDE CYP2D6 : No genetic variations were identified that p.19 extensive metabolizer would prompt changes in therapy. METOPROLOL CYP2D6 : No genetic variations were identified that p.21 extensive metabolizer would prompt changes in therapy. SIMVASTATIN SLCO1B1 : No genetic variations were identified that p.23 extensive activity would prompt changes in therapy. WARFARIN CYP2C9 : No genetic variations were identified that p.25 extensive metabolizer would prompt changes in therapy. VKORC1 : high activity GASRTOENTEROLOGY ESOMEPRAZOLE CYP2C19 : No genetic variations were identified that p.27 intermediate metabolizer would prompt changes in therapy. LANSOPRAZOLE CYP2C19 : No genetic variations were identified that p.29 intermediate metabolizer would prompt changes in therapy. OMEPRAZOLE CYP2C19 : No genetic variations were identified that p.31 intermediate metabolizer would prompt changes in therapy. ANALGESIA CODEINE CYP2D6 : No genetic variations were identified that p.33 extensive metabolizer would prompt changes in therapy. OXYCODONE CYP2D6 : No genetic variations were identified that p.35 extensive metabolizer would prompt changes in therapy. TRAMADOL CYP2D6 : No genetic variations were identified that p.37 extensive metabolizer would prompt changes in therapy. PharmaQx offers its products and services in order to better inform healthcare professionals on the genetic backgound of its clients and the link between genetics and drug response. Do not change current and/or future therapies without first consulting your doctor. © BIOGENIQ INC. 6 Date of report 2014-12-17 Sample number BIO-001-00001 NO WARNING FOR THE FOLLOWING MEDICATIONS MEDICATION ENZYME : PHENOTYPE NOTIFICATION PSYCHIATRY AMITRIPTYLINE CYP2C19 : No genetic variations were identified that p.39 intermediate metabolizer would prompt changes in therapy. CYP2D6 : extensive metabolizer ARIPIPRAZOLE CYP2D6 : No genetic variations were identified that p.41 extensive metabolizer would prompt changes in therapy. ATOMOXETINE CYP2D6 : No genetic variations were identified that p.43 extensive metabolizer would prompt changes in therapy. CLOMIPRAMINE CYP2C19 : No genetic variations were identified that