Publication Details

Title :

Use of Pharmacogenetic Drugs by the Dutch Population

Journal:

Front Genet.

Impact Factor:

3.517

Authors:

Alshabeeb MA1,2,3, Deneer VHM4, Khan A1,2, Asselbergs FW3,5,6.

Affiliations:

1 Medical Genomics Research Department, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.

2 King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

3 Division Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

4 Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands.

5 Faculty of Population Health Sciences, Institute of Cardiovascular Science, University College London, London, United Kingdom.

6 Health Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom.

Year of Publication:

2019

DOI:

10.3389/fgene.2019.00567

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.