Development of the PG PG x‐Passport: A Panel of Actionable Germline Genetic Variants for Pre‐Emptive Pharmacogenetic Testing

摘要

Pre‐emptive pharmacogenetics ( PG x) testing of a panel of germline genetic variants represents a new model for personalized medicine. Clinical impact of PG x 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 PG x testing. We, therefore, developed such a panel, hereafter called the PG x‐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 PG x‐Passport of 58 germline variant alleles, located within 14 genes ( CYP 2B6 , CYP 2C9 , CYP 2C19 , CYP 2D6 , CYP 3A5 , DPYD , F5 , HLA ‐A , HLA ‐B , NUDT 15 , SLCO 1B1 , TPMT , UGT 1A1 , and VKORC 1 ) was composed. This PG x‐Passport can be used in combination with the DPWG guidelines to optimize drug prescribing for 49 commonly prescribed drugs.