Molecular Diagnostics. Castle Medical LLC.
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1 Molecular Diagnostics Castle Medical LLC.
2 What is DNA testing? Pharmacogenomics is a scientific disciple that deals with the influence of patient s genotype on drug response. Objective: to deliver the right drug for the right patient at the right time. Pharmacogenomics is a tool that enables a switch from the one size fits all approach to a personalized therapy approach.
3 What is DNA testing? MOTHER FATHER This test is based on DNA genotyping NOT Sequencing Two copies AKA alleles of each gene. Both normal alleles Wild type (normal). One normal one mutated allele Heterozygous. Both mutated alleles Homozygous.
4 Benefits of DNA testing? Patients Physicians Health insurance companies Improve therapeutic effects Minimize unpleasant side effects Results are interesting and last a lifetime Improve safety and efficacy of the therapy Improve patients compliance (fewer side effects) Improve patients confidence in therapy Permanent takeaway information improves satisfaction Right drug to right patient minimize monetary loss. Example: Plavix Cutting-edge tech and takeaway information attracts clients
5 General introduction 1. CORE DME Panel 2. Warfarin Panel 3. Chemo Panel 4. MTHFR Test * One tube is not sufficient to get enough DNA to perform multiple tests. Please provide one tube for each test.
6 Collection technique Improper collection leads to delays and rejections. Make sure to connect with people responsible for DNA collections! Follow Castle s written instructions over those on the packaging Nothing in the mouth for 30 minutes beforehand Soak up saliva from between cheek and gum avoid teeth 30+ seconds on each side of the mouth total of at least 1 minute of collection
7 CORE DME panel (extended) CYP2D6 CYP2C9 CYP2C19 CYP3A4 CYP3A5 Common drug metabolizing enzymes tested in the old CORE DME panel CYP2B6 COMT OPRM1 SLCO1B1 New genes added to the panel
8 CORE DME panel (extended) CYP enzymes CYP (normal) Inactive products Remove from the body Active drugs Active drugs CYP (defective) Inactive products Drugs accumulate in the body Adverse effects ***To view the list of drugs affected by CYPs please go to
9 CORE DME panel (extended) CYP enzymes CYP (normal) Active products Therapeutic effect Prodrugs (inactive) CYP (defective) Active products Therapeutic failure Prodrugs (inactive) ***To view the list of drugs affected by CYPs please go to
10 CORE DME panel (extended) SLCO1B1 SLCO1B1 (normal) Drugs Inactive products Liver SLCO1B1 (defective) Drugs accumulate in the blood Liver Drugs affected: Cholesterol lowering drugs Statins. Eg. Simvastatin.
11 CORE DME panel (extended) OPRM1 OPRM1 (normal) Normal pain relief Opioid drugs OPRM1 (defective) Less pain relief Opioid drugs
12 CORE DME panel (extended) COMT COMT (normal) maintains their balance in the brain Neurotransmitters i.e Dopamine, adrenaline, serotonin Regulate Behavior, emotions, wisdom, judgment COMT (defective) leads to abnormal levels of neurotransmitters Neurotransmitters i.e Dopamine, adrenaline, serotonin Psychiatric disorders
13 Vocabulary Enzyme A protein that helps carry out a chemical reaction. Genotype What we know about a person s DNA. Helps us make predictions about their health. Phenotype The way a person actually is. Phenotypes on our reports are predictions based on patients genetics.
14 Core DME Sample Report
15 Core DME: Recommendations
16 Core DME: Inducers and Inhibitors Some drugs and plants can speed up or slow down the action of drug metabolizing enzymes. They can do this by sticking to enzymes directly or by causing cells to make more or less of an enzyme. This is one of the causes of drug interactions like taking statins with grapefruit juice.
17 Warfarin panel Warfarin is an anticoagulant used in thromboembolic disease. Too much warfarin. Excessive bleeding. Possible death Good target level of warfarin Too little warfarin. Clot formation. Possible death *Due to different genetic makeup every individual has different capacity to respond towards warfarin
18 Warfarin panel VKORC1 CYP2C9 GGCX CYP4F2 CACNA1C Regulate warfarin response Castle s warfarin panel results Add in Right dose of warfarin based on patient s genetic makeup
19 Warfarin panel
20 Warfarin panel Warfarin panel
21 MTHFR test What is MTHFR? This enzyme plays a critical role in vitamin-b12 and folate metabolism. What are consequences of Genetic defect in MTHFR gene? Less efficient enzyme activity that can lead to elevated homocysteine (a potentially toxic amino acid) levels. What are consequences of high homocysteine levels? Increase risk of developing cardiovascular disorders, psychiatric disorders, cancer, osteoporosis and pregnancy complications.
22 MTHFR test MTHFR DNA test Ora Collect Buccal swab AND OR Homocysteine quantification Urine sample Blood sample *Before collecting urine/blood samples, fasting for at least 12 hours is recommended.
23 MTHFR test Target clinics Cardiology clinics- This test is specially relevant for people who have a personal or family history of premature cardiovascular disease or thrombosis. It may also be ordered when a close relative has MTHFR gene mutations. Maternity hospitals- Prospective mothers with a history of miscarriages are also advised to go for this test.
24 MTHFR test..
25 MTHFR test..
26 In the Future Expanded Core panel is validated and will replace the old panel in early September Sequencer is running but not validated for clinical tests will test BRCA1, BRCA2 and PALB2 Tests on the new Core panel came from your and clinics suggestions. Keep them coming!
27 Thanks for listening! Any questions?
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