University of Utah Department of Human Genetics Pharmacogenomics Louisa A. Stark, Ph.D. Director.
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Transcript of University of Utah Department of Human Genetics Pharmacogenomics Louisa A. Stark, Ph.D. Director.
![Page 1: University of Utah Department of Human Genetics Pharmacogenomics Louisa A. Stark, Ph.D. Director.](https://reader030.fdocuments.us/reader030/viewer/2022033107/56649db55503460f94aa6391/html5/thumbnails/1.jpg)
University of UtahDepartment of Human Genetics
PharmacogenomicsLouisa A. Stark,
Ph.D. Director
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Adverse drug reactions
• Every year, over 106,000 people in the United States die from adverse reactions to correctly prescribed doses of drugs.
• Another 2.2 million suffer serious, but not deadly, side effects.
A major health issue
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• 4th leading cause of death in the U.S.• 15% of U.S. hospital admissions• $136 billion in medical costs (2001)
• 80-85% of drug response is due to genetics
Adverse drug reactions
A major health issue
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• First emerged around the 1950’s
• Scientists began to notice that different responses to drugs ran in families and ethnic groups.
Field of pharmacogenetics
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Tour of the Basics
DNA: The basis of genetics
DNACell
Chromosomes
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• We are all 99.9% similar in our DNA. • Individuals vary by only 0.1%
• Individual variations may correlate with different responses to medicines and magnitude of disease risk.
Human Genome Project data
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Pharmacogenetics
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Goal of pharmacogenetics
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SNPs: The key to pharmacogenetics
SNiPping Away at the Problem
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• Break down more than 30 classes of drugs– Beta-blockers, tricyclic
antidepressants, morphine derivates, antiarrhythmics, etc.
• Poor metabolizers – need lower dose– 6% of Caucasians– 2% of African Americans– 1% of Asians
• Ultra-rapid metabolizers – need higher dose– 20% of Ethiopians– 7% of Spanish– 1.5% of Scandinavians
Liver enzymes
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Pharmacogenetics today: leukemia
Chemotherapy for leukemia
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• 5-flurouracil (5-FU)- Chemotherapy agent- Stops tumor formation- Used to treat colorectal, breast, lung, cervical,
neck and head cancer- Effective for 20-30% of patients with colorectal
cancer- Genotype predicts treatment effectiveness
- Patients with 1 genotype are 5 times more likely to respond successfully to treatment with 5-FU than patients with another genotype
Pharmacogenetics today: cancer
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• 4 major statin drugs for lowering cholesterol
• Clinical trial looking for genetic associations in patient response to each drug
• Of 10,000 people in Iceland taking statins, 2,000 do not respond and are related to each other
Pharmacogenetics today: cholesterol
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Future applications: depression
• Three high school students, Marti, Toni, and Brianna, sought treatment for depression. Their doctor prescribed nortriptyline, a common antidepressant medication.
• After taking the medication for a month, Marti felt much better. She had few episodes of depression and no adverse reactions to the drug.
• Toni's depression also had subsided. However, she could not sleep and often felt nauseated and anxious.
• The medication didn't do much for Brianna: she felt neither better nor worse and had no adverse reactions to the drug.
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Gene expression
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Gene expression: application to obesity
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• Create diagnostic tests to predict whether a patient has a genetic predisposition to obesity. – Examine the DNA sequence of a person's obesity-related
genes to detect genetic signatures that predict a predisposition to obesity.
– Examine a tissue sample for abnormal gene expression patterns that indicate a predisposition to obesity.
• Design drugs intended to treat or prevent
obesity. – Develop drugs that inhibit the function of proteins related to
obesity.
• Design drugs to control expression of obesity genes.– Drugs would interact directly with DNA in key cells and tissues
to prevent genes from being turned on or off.
Gene expression: application to obesity
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• People vary in their risk of getting certain diseases.
• Example:– Two 15-year-old boys are the
same height and weight, with similar diet and exercise habits.
– Determine risk for developing diabetes.
Determining disease risk
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• New, more accurate diagnostic tests– Predict a patient's response to
specific drugs based on his or her genetic profile.
Benefits of pharmacogenetics
•Personalized drug therapies–Match a patient with effective and safe medications based on information from diagnostic tests.
•Personalized disease prevention strategies
–Developed using genetic tests that estimate a patient's risk of getting a particular disease, combined with personalized drug therapies.
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Pharmacogenetics: public health issues
• Population-based screening tests- How will we weigh the medical and economic
benefits of genotyping all individuals in order to direct an intervention to only a few?
- Example: Women with the factor V Leiden allele who use oral contraceptives are at greatly increased risk of venous thrombosis. Should all women be tested for this allele before beginning to take oral contraceptives?
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Issues related to pharmacogenetics
• Drug development for less-common SNP profiles- Who will pay for development of less profitable drugs?
• Insurance and Medicaid coverage - Will potentially expensive diagnostic tests be covered?
• Education of health care providers - How will providers be trained to understand new
diagnostic tests and use them when treating and advising patients?
• Ethical and privacy issues- Who will have access to genetic information and
databases? - How do families handle conflicts when one person
wants to be tested and others do not?- Should parents decide whether their children should be
tested?
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Genetic Science Learning Center Website
http://gslc.genetics.utah.eduhttp://gslc.genetics.utah.edu
To learn more about pharmacogenomics
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