Leiden University Scholarly Publications

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Wouden, C.H. van der; Rhenen, M.H. van; Jama, W.O.M.; Ingelman-Sundberg, M.; Lauschke, V.M.; Konta, L.; ... ; Guchelaar, H.J. (2019)

Development of the PGx-Passport: A Panel of Actionable Germline Genetic Variants for Pre-Emptive Pharmacogenetic Testing

Article / Letter to editor
Pre-emptive pharmacogenetics (PGx) testing of a panel of germline genetic variants represents a new model for personalized medicine. Clinical impact of PGx testing is maximized when all variant alleles for which actionable clinical guidelines are available are included in the test panel. However, no such standardized panel has been presented to date, impeding adoption, exchange, and continuity of PGx testing. We, therefore, developed such a panel, hereafter called the PGx-Passport, based on the actionable Dutch Pharmacogenetics Working Group (DPWG) guidelines. Germline-variant alleles were systematically selected using predefined criteria regarding allele population frequencies, effect on protein functionality, and association with drug response. A PGx-Passport of 58 germline variant alleles, located within 14 genes (CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, DPYD, F5, HLA-A, HLA-B, NUDT15, SLCO1B1, TPMT, UGT1A1, and VKORC1) was composed. This PGx-Passport can be used in combination...Show morePre-emptive pharmacogenetics (PGx) testing of a panel of germline genetic variants represents a new model for personalized medicine. Clinical impact of PGx testing is maximized when all variant alleles for which actionable clinical guidelines are available are included in the test panel. However, no such standardized panel has been presented to date, impeding adoption, exchange, and continuity of PGx testing. We, therefore, developed such a panel, hereafter called the PGx-Passport, based on the actionable Dutch Pharmacogenetics Working Group (DPWG) guidelines. Germline-variant alleles were systematically selected using predefined criteria regarding allele population frequencies, effect on protein functionality, and association with drug response. A PGx-Passport of 58 germline variant alleles, located within 14 genes (CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, DPYD, F5, HLA-A, HLA-B, NUDT15, SLCO1B1, TPMT, UGT1A1, and VKORC1) was composed. This PGx-Passport can be used in combination with the DPWG guidelines to optimize drug prescribing for 49 commonly prescribed drugs.Show less
All authors
Wouden, C.H. van der; Rhenen, M.H. van; Jama, W.O.M.; Ingelman-Sundberg, M.; Lauschke, V.M.; Konta, L.; Schwab, M.; Swen, J.J.; Guchelaar, H.J.
Date
2019-10-01
Journal
Clinical Pharmacology and Therapeutics
Volume
106
Issue
4
Pages
866 - 873
DOI
doi:10.1002/cpt.1489