Abstract
IntroductionThe 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.MethodsUsage 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.ResultsOver 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.ConclusionPGX 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.
Highlights
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
This study aimed to determine (1) the major genes involved in drug-gene interactions, (2) the percentage of Dutch population using the drugs listed by DPWG and frequency of genetic variants that affect PGX drugs, in addition to (3) identifying the main prescribed PGX drug category
The average MAF of CYP2C9∗3 among the tested samples for the other 17 European countries was 0.08 which is consistent to MAF found in GoNL
Summary
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. Genotypes with potential interactions with certain drugs that necessitate therapeutic intervention or modification such as increasing or decreasing drug dose, stopping the drug or using an alternative are titled as actionable genotypes (Bain et al, 2018) These medications which show variable effects based on patients’ genetic traits can be described as pharmacogenetic (PGX) drugs (Carpenter et al, 2016). Action of important therapeutic classes of drugs such as anticoagulants, anti-infective agents, and some pain relievers was confirmed to be affected by multiple interactions with numerous genetic variations Carriage of such variations may put patients at risk of developing adverse drug reactions (ADRs) (Collins et al, 2016)
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