Pharmacogenetics

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.

IMPORTANCE OF GETTING TESTED

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.

OUR PHARMACOGENETIC SERVICES

Counseling of physicians & patients

Drug metabolism & interaction check

Routine genetic testing & test development

Panel diagnostics for clinical studies

ORDER FORM

Download here

ACCEPTED MATERIAL

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.

TURNAROUND TIME

Results available in 1-2 weeks from sample receipt

TECHNOLOGY

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).

Test Methodology

Sequencing

Next generation
sequencing (Illumina)

Enrichment

Twist Human Core
Exome plus Ref Seq
Spikeln

SNV and CNV data anlaysis

Illumina DRAGEN
Bio-IT Platform

Data Evaluation

VarSeq by
GoldenHelix

Reference Genome

hg38, NCBI GR38

Quality Criteria