It is well known, that there are interindividual differences in response to xenobiotics. One of the factors contributing to these differences in drug response are genetic variants influencing the expression and function of genes involved in drug metabolism.

To determine the impact of genetic variants there are multiple possible approaches:

1.       Functional assessment of variants of a selected gene on its expression or function in in vitro experiments [1, 2, 3, 4]

2.       Clinical and/or cohort studies testing the influence of genetic variants on drug efficacy and/or exposure [5, 6, 7]

3.       Testing of genetic variants in cases of adverse drug reactions or treatment failure [8, 9, 10]

Within the program, we are testing the influence of naturally occurring genetic polymorphisms on selected mechanisms associated with drug metabolism and or drug efficacy.

In close collaboration with our clinical partners https://pharma.unibas.ch/de/research/research-groups/pharmaceutical-care-2170/research/pharmacogenotyping/, we are investigating the procedure and applicability of pharmacogenetic panel testing in pharmaceutical care (community pharmacy and hospital pharmacy). Within the collaborative project, we initially gathered the pharmacogenetic information in the Summary of product characteristics of substances currently available on the Swiss market [11], whereby supplementing the information provided at https://www.pharmgkb.org/labelAnnotations. The applicability is now investigated in a case serious and a clinical study.

The group is part of the Swiss Personalized Health Network (https://sphn.ch/network/project-overview/) infrastructure project SwissPKcdw (https://sphn.ch/wp-content/uploads/2019/11/2018DEV21_SwissPKcdw_Lay_summary_final.pdf) in which we generated an infrastructure that can be used in national research projects with pediatric patients to optimize pediatric dosage regimens with pharmacokinetic modeling.

[1] Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional characterization, interaction with OCT2 (SLC22A2), and single nucleotide polymorphisms. Meyer zu Schwabedissen HE, Verstuyft C, Kroemer HK, Becquemont L, Kim RB. Am J Physiol Renal Physiol. 2010;298(4):F997-F1005. doi: 10.1152/ajprenal.00431.2009. (https://www.ncbi.nlm.nih.gov/pubmed/20053795 )

[2] PDZ domain containing protein 1 (PDZK1), a modulator of membrane proteins, is regulated by the nuclear receptor THRβ. Ferreira C, Prestin K, Hussner J, Zimmermann U, Meyer zu Schwabedissen HE. Mol Cell Endocrinol. 2018; 461:215-225. doi: 10.1016/j.mce.2017.09.017. (https://www.ncbi.nlm.nih.gov/pubmed/28928085 )

[3] Functional assessment of genetic variants located in the promoter of SHP1 (NR0B2). Prestin K, Olbert M, Hussner J, Völzke H, Meyer zu Schwabedissen HE. Pharmacogenet Genomics. 2017 (11):410-415. doi: 10.1097/FPC.0000000000000310. (https://www.ncbi.nlm.nih.gov/pubmed/28873070)

[4] Genetic variants of SLCO1B7 are of relevance for the transport function of OATP1B3-1B7. Meyer zu Schwabedissen HE, Seibert I, Grube M, Alter CL, Siegmund W, Hussner J. Pharmacol Res. 2020 Nov;161:105155. doi: 10.1016/j.phrs.2020.105155. (https://pubmed.ncbi.nlm.nih.gov/32818652/)

[5] Function-impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify the therapeutic efficacy of statins in a population-based cohort. Meyer zu Schwabedissen HE, Albers M, Baumeister SE, Rimmbach C, Nauck M, Wallaschofski H, Siegmund W, Völzke H, Kroemer HK. Pharmacogenet Genomics. 2015; 25(1):8-18. doi: 10.1097/FPC.000000000000009 (https://www.ncbi.nlm.nih.gov/pubmed/25379722 )

[6] No major role of norepinephrine transporter gene variations in the cardiostimulant effects of MDMA. Vizeli P, Meyer zu Schwabedissen HE, Liechti ME. Eur J Clin Pharmacol. 2018;74(3):275-283. doi: 10.1007/s00228-017-2392-2. (https://www.ncbi.nlm.nih.gov/pubmed/29198060 )

[7] Role of Serotonin Transporter and Receptor Gene Variations in the Acute Effects of MDMA in Healthy Subjects. Vizeli P, Meyer zu Schwabedissen HE, Liechti ME. ACS Chem Neurosci. 2019;10(7):3120-3131. doi: 10.1021/acschemneuro.8b00590 (https://pubmed.ncbi.nlm.nih.gov/30589533/ )

[8] Creatine kinase elevation caused by a combination of fluvastatin and telmisartan in a patient heterozygous for the CYP2C9*3 and ABCC2 -24C > T variants: a case report. Meyer zu Schwabedissen HE, Siegmund W, Kroemer HK, Rollnik JD. BMC Res Notes. 2014;7:688. doi: 10.1186/1756-0500-7-688 (https://www.ncbi.nlm.nih.gov/pubmed/25280537)

[9] Nonresponse to high-dose bupropion for depression in a patient carrying CYP2B6*6 and CYP2C19*17 variants: a case report. Stäuble CK, Lampert ML, Mikoteit T, Hatzinger M, Hersberger KE, Meyer zu Schwabedissen HE. Pharmacogenomics. 2020; 21(16):1145-1150. doi: 10.2217/pgs-2020-0087 (https://pubmed.ncbi.nlm.nih.gov/33124517/ )

[10] Jeiziner C, Stäuble CK, Lampert ML, Hersberger KE, Meyer zu Schwabedissen HE. Enriching Medication Review with a Pharmacogenetic Profile – A Case of Tamoxifen Adverse Drug Reactions. Pharmgenomics Pers Med. 2021;14:279-286 (https://doi.org/10.2147/PGPM.S285807)

[11] Pharmacogenetic information in Swiss drug labels - a systematic analysis. Jeiziner C, Suter K, Wernli U, Barbarino JM, Gong L, Whirl-Carrillo M, Klein TE, Szucs TD, Hersberger KE, Meyer zu Schwabedissen HE. Pharmacogenomics J. 2020. doi: 10.1038/s41397-020-00195-4. (https://pubmed.ncbi.nlm.nih.gov/33070160/)