eprintid: 10082336 rev_number: 18 eprint_status: archive userid: 608 dir: disk0/10/08/23/36 datestamp: 2019-09-26 09:02:25 lastmod: 2021-11-30 23:03:27 status_changed: 2019-09-26 09:02:25 type: article metadata_visibility: show creators_name: Alshabeeb, MA creators_name: Deneera, VHM creators_name: Khan, A creators_name: Asselbergs, FW title: Use of Pharmacogenetic Drugs by the Dutch Population ispublished: pub divisions: UCL divisions: B02 divisions: DD4 keywords: pharmacogenetics, preemptive genetic testing, ADRs, CYP2D6, SLCO1B1, CYP2C19 note: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. https://creativecommons.org/licenses/by/4.0/ abstract: Introduction: The Dutch Pharmacogenetics Working Group (DPWG) indicated a list of actionable genotypes that affect patients’ response to more 50 drugs; these drugs which show variable effects based on patients’ genetic traits were named as pharmacogenetics (PGX) drugs. Preemptive genetic testing before using these drugs may protect certain patients from serious adverse reactions and could help in avoiding treatment failures. The objectives of this study include identifying the rate of PGX drug usage among Dutch population, estimating the level of users who carry the actionable genotypes and determining the main genes involved in drug’s effect variability. Methods; Usage of PGX drugs over 2011–2017 by the insured population (an average of 11.4 million) in outpatient clinics in Netherlands was obtained from the publically available GIP databank. The data of 45 drugs were analyzed and their interactions with selected pharmacogenes were estimated. Frequency of actionable genotypes of 249 Dutch parents was obtained from the public database: Genome of Netherlands (GoNL), to identify the pattern of genetic characteristics of Dutch population. Results: Over a 7 year period, 51.3 million exposures of patients to PGX drugs were reported with an average of 5.3 exposures per each drug user. One quarterof the exposures (12.4 million) are predicted to be experienced by individuals with actionable genotypes (risky exposures). Up to 60% of the risky exposures (around 7.5 million) were related to drugs metabolized by CYP2D6. SLCO1B1, and CYP2C19 were also identified among the top genes affecting response of drugs users (involved in about 22 and 12.4% of the risky exposures, respectively). Cardiovascular medications were the top prescribed PGX drug class (43%), followed by gastroenterology (29%) and psychiatry/neurology medications (15%). Women use more PGX drugs than men (55.8 vs. 44.2%, respectively) with the majority (84%) of users in both sexes are above 45 years. Conclusion: PGX drugs are commonly used in Netherlands. Preemptive panel testing for CYP2D6, SLCO1B1, and CYP2C19 only could be useful to predict 95% of vulnerable patients’ exposures to PGX drugs. Future studies to assess the economic impact of preemptive panel testing on patients of older age are suggested. date: 2019-07 date_type: published publisher: FRONTIERS MEDIA SA official_url: https://doi.org/10.3389/fgene.2019.00567 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1673026 doi: 10.3389/fgene.2019.00567 lyricists_name: Asselbergs, Folkert lyricists_id: FASSE08 actors_name: Kalinowski, Damian actors_id: DKALI47 actors_role: owner full_text_status: public publication: Frontiers in Genetics volume: 10 article_number: 567 pages: 9 issn: 1664-8021 citation: Alshabeeb, MA; Deneera, VHM; Khan, A; Asselbergs, FW; (2019) Use of Pharmacogenetic Drugs by the Dutch Population. Frontiers in Genetics , 10 , Article 567. 10.3389/fgene.2019.00567 <https://doi.org/10.3389/fgene.2019.00567>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10082336/1/Asselbergs_Use%20of%20Pharmacogenetic%20Drugs%20by%20the%20Dutch%20Population_VoR.pdf