OVERVIEW
Pharmacogenetics examines how a person’s genetic makeup can affect their response to medication, and predict whether they may experience side effects, like adverse drug reaction (ADR). ADR or therapy resistance can result from individual genetic differences in the genes coding for transporter proteins, enzymes, or drug targets. Variants in the corresponding genes can lead to altered metabolic rates (see figure) and impaired transport or binding capacity which can eventually lead to altered drug efficacy and tolerability.
Pharmacogenetic testing can identify these variants and the results can improve the safety and effectiveness of drug therapy by tailoring treatment to a person’s specific genetic profile and optimizing their drug dosage and care.
Pharmacogenetics can help identify genetic factors that may affect a person’s response to a particular drug, thereby, enabling the determination of the most appropriate medication and dosage. This can be especially important for people with negative experiences with medications in the past or who are at higher risk for certain side effects.
It is important to note that, in some cases, the results of a pharmacogenetic test may not change treatment recommendations. We offer pharmacogenetic consultation to discuss potential benefits and limitations of testing.
WHO COULD BENEFIT FROM THIS TEST
Patients with conspicuous findings in therapeutic drug monitoring
Patients who are about to undergo planned therapy with a drug for which the summary of product characteristics strongly recommends genetic testing before treatment
Patients who have to undergo long term therapy with known difficult-to-adjust medication (e.g., psychotropic drug therapy)
Patients who suffer ADR or therapy resistance that are not due to drug/food interactions, allergies, etc.
| Indication | Drug |
| ANALGESICS | Morphine prodrugs (CYP2D6), NSAIDs (CYP2C9) |
| ANESTHESIA INTOLERANCE | Malignant hyperthermia (RYR1, CACNA1S), Postoperative apnea (BCHE) |
| CORONARY ARTERY DISEASE/METABOLIC SYNDROME/DIABETES | β-blockers (CYP2D6), Clopidogrel (CYP2C19), Mavacamten (CYP2C19), Statins (SLCO1B1), Sartans (CYP2C9), Sulfonylureas (CYP2C9), Warfarin/Phenprocuomon (CYP2C9, VKORC1) |
| INBORN ERRORS OF METABOLISM | Eliglustat – Gaucher disease (CYP2D6), Migalastat – Fabry disease (GLA), Tezacaftor/Ivacaftor/Elecacaftor – cystic fibrosis (CFTR) |
| MULTIPLE SCLEROSIS | Siponimod (CYP2C9) |
| ONCOLOGY | Azathioprine (TPMT), Fluorouracil (DPYD), Irinotecan (UGT1A1), Paclitaxel (CYP2C8), Sacituzumab govitecan (UGT1A1), Tamoxifen (CYP2D6) |
| PSYCHOPHARMACOLOGY | Antiepileptic drugs (CYP2C9), Dopamine (COMT), Multidrug resistance (ABCB1=MDR1), Psychotropic drugs (CYP2D6, CYP2C19, CYP3A5, CYP1A2, CYP3A4) |
| VIROLOGY/BACTERIOLOGY | Abacavir (HLA-B), Efavirenz (CYP2B6), Peginterferon (IFNL3, ITPA), Sulfonamides (NAT2) |
OUR TESTS
If an ADR due to a genetic cause is suspected, genetic testing is recommended. Each patient should be considered individually since variants in different enzymes, transporters, or targets, can influence the efficacy of different drugs. There is no “one test fits all” drug tolerance test.
Please note: current or planned medications should be listed on the order form, genes to be tested should be clearly stated on the order form (if not known, a consultation is offered – see below).
CONSULTATION
We offer pharmacogenetic testing since 2001. As the selection of a specific genetic test can be complex, we offer a detailed and free-of-charge pharmacogenetic consultation. This includes the examination of possible drug interactions in patients taking multiple medications or interpreting the results of therapeutic drug monitoring in the context of pharmacogenetic diagnostics. Thus, it is possible to determine which examinations are useful for clarifying the medical question before the test. In addition, a consultation can also be sought after receiving the results.
1
Counseling of physicians & patients
2
Drug metabolism & interaction check
3
Routine genetic testing & test development
4
Panel diagnostics for clinical studies
1-2 ml EDTA Blood
Since it is a genetic test, drug intake does not affect the test result. Preliminary testing (e.g. therapeutic drug monitoring) is desirable, but not mandatory.
Please note: DO NOT FREEZE. Ship with a frozen ice pack. Prepare the package such that the tube is tightly packed and not loose. Avoid getting the blood tube wet from the ice pack. Place a paper towel in between ice pack and blood tube if necessary. In sub-zero temperatures, include an unfrozen ice pack in the shipping container as insulation.
Results available in 1-2 weeks from sample receipt
DNA is isolated and next generation sequencing is performed on all coding exons and conserved intronic regions. Single base pair changes, small deletions and duplications and copy number variants (CNV) are identified. Sequencing runs result in a Quality Score of >30 (accuracy >99.9%) in at least 75% of all bases with a coverage of >20-fold. CNV detection sensitivity is 76.99% and precision is 62.59% (with GC limitation between 0.4 and 0.6 per target sensitivity is 77.04% and precision is 84.10%). Variant classification is performed following ACMG guidelines (Richards et al. 2015, Genet Med 17:405; Kearney et al. 2011, Genet Med 13:680).
Next generation
sequencing (Illumina)
Twist Human Core
Exome plus Ref Seq
Spikeln
Illumina DRAGEN
Bio-IT Platform
VarSeq by
GoldenHelix
hg38, NCBI GR38
>30 (precision >99,9%)
in min. 75% of bases
99.92-99.93%; confirmation of reported SNV with Sanger
sequencing, data analysis with
SeqPilot
Richards et al. 2015, Genet Med
17:405; Ellard et al. “ACGS Best
Practice Guidelines for Variant
Classification 2020″
MaxEntScan,
SpliceSiteFinder-like,
REVEL
HGMD Professional
release, ClinVar,
gnomAD
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