Drugs & Genetics: Why Do Some People Respond to Drugs Differently than Others?

1. Drugs & Genetics: Why Do Some People Respond to Drugs Differently than Others? Bilal Mohammed

2. Purpose/problem • The purpose of this problem is to determine why some gene mutations cause people to respond differently to a drug.

3. Background research • From 2005 to 2008, 48% of everyone in the U.S. was using at least one prescription drug. Prescription drugs can be very dangerous, because of all the different reactions people have to those prescription drugs. Most of those reactions have to genetic mutation. Genetic mutation is any event that changes genetic structure.

4. hypothesis • if people react differently then they have different genetics and that results to different genetic mutations and that’s why people have different reactions.

5. materials • Computer with an internet connection • PharmGKB online account.

6. procedures • First, go to the PharmGKB Pharmacogenomics Knowledge Base Tutorial and follow the steps through the section titled "How can I look up a drug and find out more information on it?". • On step 5 of the tutorial section, for clopidogrel and other drugs that you investigate, read through the information in the "Overview" tab. • What does the entry on clopidogrel tell you about its medical use? What kind of patients would use clopidogrel? How does the drug function, in general? • For each drug that you investigate, record in your lab notebook the following information: • The generic and trade (brand) names of the drug. • What kind of chemical the drug is, and what other drugs it is related to. You may want to draw its chemical structure. • What medical condition the drug is used to treat. • The drug's general effect on the body. • Click on the "Properties" tab to read more information about how the drug functions on a molecular level. • =in the "Pathways" tab. There may be a lot of alleles listed, and they may not all be of genes that were covered in the "Pathways" tab. • For example, for clopidogrel in the "Clinical Annotations" tab you will find an allele of the CYP2C19 gene. The rsID rs424485 will be there, and the "Relevance" listed for this allele should be similar or related to its description you read in the "Pathways" tab. • If the "Pathways" tab did not give information on alleles and rsIDs for a drug that you are investigating, when looking at each allele listed in the "Clinical Annotations" tab, within the "Clinical PGx" tab, pay special attention to the gene name (under "Gene"), the allele's rsID (under "Position"), and the description of how they are related to the drug (under "Relevance"). • Look at the "Pathways" tab again and locate the allele's gene name. How does the protein this gene encodes for interact with the drug in the pathway? • How do you think the change in the allele affects how the body responds to the drug? • To find additional information on the gene alleles that are associated with a varied response to the drug, continue through the tutorial by exploring the information available in the "Is Related To" tab (steps 6 to 8).

7. Data • Plavix: (trade names) Clopidogrel, Clopidogrel sulfate, Plavix • Uses: is used to reduce atherosclerotic events such as myocardial infarction, stroke, and vascular death in patients who have had a recent stroke. • Lipitor: (trade names) Lanvis, Tabloid, Wellcome U3B • Uses: The drug is used in the therapy of acute leukemia

8. conclusion • My hypothesis was correct when I stated that if people have different genetics they will have different genetic mutations and have different reactions.