Abstract
Aligned with the mission of the Dutch Pharmacogenetics Working Group (DPWG) to promote the implementation of pharmacogenetics (PGx), this guideline is specifically designed to optimize pharmacotherapy of cholesterol lowering medication (statins) and glucose lowering medication (sulfonylureas). The SLCO1B1 c.521 T > C variant reduces the activity of the SLCO1B1 transporter involved in statin transport out of the blood into the liver. High blood concentrations of statins increase the risk of serious myopathy. For simvastatin, the DPWG recommends choosing an alternative in homozygotes for these gene variant and to preferably choose an alternative in heterozygotes. For atorvastatin, the DPWG recommends to preferably choose an alternative in carriers of this gene variant having additional risk factors for myopathy. For rosuvastatin, the DPWG recommends keeping the dose as low as possible in carriers of this gene variant with additional risk factors. No therapy adjustment is required for fluvastatin and pravastatin in carriers of this gene variant. Gene variants can diminish the activity of the enzyme CYP2C9, that converts sulfonylurea to less effective metabolites. Although CYP2C9 gene variants may lead to increased levels of glibenclamide, gliclazide, glimepiride, and tolbutamide, no therapy adjustments are required in patients with these variants. The main reason is that there was either no negative clinical effect or an increase in hypoglycemic, which is of less importance than the increase in effectiveness it signals. The DPWG classifies pre-emptive SLCO1B1 testing as ‘essential’ for simvastatin 80 mg/day, ‘beneficial’ for simvastatin up to 40 mg/day, and ‘potentially beneficial’ for atorvastatin and rosuvastatin.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
269,00 € per year
only 22,42 € per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
All data and material are either included in the supplementary information or publicly available (i.e. the published articles, PubMed). The guidelines and background information are available on KNMP.nl [14] and will be available on PharmGKB.org.
References
Swen JJ, Huizinga TW, Gelderblom H, de Vries EG, Assendelft WJ, Kirchheiner J, et al. Translating pharmacogenomics: challenges on the road to the clinic. PLoS Med. 2007;4:e209.
Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, et al. Pharmacogenetics: from bench to byte-an update of guidelines. Clin Pharm Ther. 2011;89:662–73.
Swen JJ, Nijenhuis M, van Rhenen M, de Boer-Veger NJ, Buunk AM, Houwink EJF, et al. Pharmacogenetic information in clinical guidelines: the European perspective. Clin Pharm Ther. 2018;103:795–801.
European Association for Clinical Pharmacology and Therapeutics (EACPT). Available from: https://www.eacpt.eu/.
European Association of Hospital Pharmacists (EAHP). Available from: https://www.eahp.eu/.
Vinci P, Panizon E, Tosoni LM, Cerrato C, Pellicori F, Mearelli F, et al. Statin-associated myopathy: emphasis on mechanisms and targeted therapy. Int J Mol Sci. 2021;22:11687.
Vrablik M, Zlatohlavek L, Stulc T, Adamkova V, Prusikova M, Schwarzova L, et al. Statin-associated myopathy: from genetic predisposition to clinical management. Physiol Res. 2014;63:S327–34.
Alfirevic A, Neely D, Armitage J, Chinoy H, Cooper RG, Laaksonen R, et al. Phenotype standardization for statin-induced myotoxicity. Clin Pharm Ther. 2014;96:470–6.
National Center for Biotechnology Information (NCBI). SLCO1B1 solute carrier organic anion transporter family member 1B1 [Homo sapiens (human)]; Available from: https://www.ncbi.nlm.nih.gov/gene/10599.
Niemi M, Pasanen MK, Neuvonen PJ. Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharm Rev. 2011;63:157–81.
Romaine SP, Bailey KM, Hall AS, Balmforth AJ. The influence of SLCO1B1 (OATP1B1) gene polymorphisms on response to statin therapy. Pharmacogenomics J. 2010;10:1–11.
Manson LEN, Nijenhuis M, Soree B, de Boer-Veger NJ, Buunk AM, Houwink EJF, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of CYP2C9, HLA-A and HLA-B with anti-epileptic drugs. Eur J Hum Genet. 2024;32:903–11.
Swen JJ, Wilting I, de Goede AL, Grandia L, Mulder H, Touw DJ, et al. Pharmacogenetics: from bench to byte. Clin Pharm Ther. 2008;83:781–7.
Royal Dutch Pharmacists Association (KNMP). Pharmacogenetic Recommendation Text. Available from: https://www.knmp.nl/.
Karamperis K, Koromina M, Papantoniou P, Skokou M, Kanellakis F, Mitropoulos K, et al. Economic evaluation in psychiatric pharmacogenomics: a systematic review. Pharmacogenomics J. 2021;21:533–41.
Simeonidis S, Koutsilieri S, Vozikis A, Cooper DN, Mitropoulou C, Patrinos GP. Application of economic evaluation to assess feasibility for reimbursement of genomic testing as part of personalized medicine interventions. Front Pharm. 2019;10:830.
Bank PCD, Caudle KE, Swen JJ, Gammal RS, Whirl-Carrillo M, Klein TE, et al. Comparison of the guidelines of the clinical pharmacogenetics implementation consortium and the Dutch pharmacogenetics working group. Clin Pharm Ther. 2018;103:599–618.
Cooper-DeHoff RM, Niemi M, Ramsey LB, Luzum JA, Tarkiainen EK, Straka RJ, et al. The Clinical Pharmacogenetics Implementation Consortium Guideline for SLCO1B1, ABCG2, and CYP2C9 genotypes and Statin-Associated Musculoskeletal Symptoms. Clin Pharm Ther. 2022;111:1007–21.
Acknowledgements
We want to thank Anna de Goede for performing the first systematic review for tolbutamide in 2006 and Yasmina Laouti for performing the second systematic reviews for atorvastatin and fluvastatin in 2020.
Funding
This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 668353. The DPWG received funding from the Royal Dutch Pharmacists Association.
Author information
Authors and Affiliations
Contributions
DFGJW drafted the manuscript. EJHF supervised drafting of the manuscript and contributed to conceiving the work and interpretation of the results. MN performed most of the literature searches and article summaries and suggested clinical decision support texts. BS had the clinical decision support texts translated in English and published them. NBV, AB, HJG, AR, GAR, RHNS, JJS, DT, and RW contributed to conceiving the work and interpretation of the results. VHMD led the meetings in which the DPWG decided about the article summaries and clinical decision supports texts and contributed to conceiving the work and interpretation of the results. In addition, all authors revised the manuscript and approved the final version.
Corresponding author
Ethics declarations
Competing interests
The Pharmacogenetics Working Group of the KNMP (DPWG) formulates the optimal recommendations for each phenotype group based on the available evidence. If this optimal recommendation cannot be followed due to practical restrictions, e.g. therapeutic drug monitoring or a lower dose is not available, then the health care professional should consider the next best option.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Wolthuis, D.F.G.J., Nijenhuis, M., Soree, B. et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between SLCO1B1 and statins and CYP2C9 and sulfonylureas. Eur J Hum Genet 33, 413–420 (2025). https://doi.org/10.1038/s41431-024-01769-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41431-024-01769-7
This article is cited by
-
Two for the heart: Dutch Pharmacogenetic Working Group prescribing guidance on statins and sulfonylureas to reduce cardiometabolic risk
European Journal of Human Genetics (2025)
