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A common polymorphism in the ABCB1 gene is associated with side effects of PGP-dependent antidepressants in a large naturalistic Dutch cohort

The Pharmacogenomics Journal volume 16, pages 202–208 (2016)Cite this article

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Abstract

The drug efflux transporter permeability glycoprotein (PGP) and cytochrome P450 (CYP) 2C19 are important for eliminating antidepressants from the brain and body. The ABCB1 gene, encoding for PGP, and CYP2C19 gene have several variants that could influence enzyme function and thereby the effect of PGP- and 2C19-dependent antidepressants. We investigated the association of antidepressant side effect and common genetic variation in 789 antidepressant users. In PGP-dependent antidepressant users, the A-allele of the rs2032588 single-nucleotide polymorphism (SNP) was associated with a lower number of side effects after adjusting for gender, age, dosage and duration of use, (B=−0.44, q=4.6 × 10−3). This association was different from and absent in non-PGP-dependent antidepressant users. Other SNP associations as well as an interaction analysis between the rs2032588 SNP and the CYP2C19 SNPs were not statistically significant after adjusting for covariates and multiple comparisons. The association of rs2032588 with antidepressant side effects suggests the involvement of the ABCB1 genotype in the clinical pharmacology of PGP-dependent antidepressants.

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Acknowledgements

The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organizations VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, Scientific Institute for Quality of Healthcare (IQ healthcare), the Netherlands Institute for Health Services Research (NIVEL) and the Netherlands Institute of Mental Health and Addiction (Trimbos). The funding agents were not involved in the design or conduct of the study or in the collection, management, analysis, or interpretation of the data, or preparation, review, or approval of the manuscript.

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Author notes

  1. P M Bet and E C Verbeek: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands

    P M Bet, D B M Straver & J G Hugtenburg

  2. Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands

    P M Bet, B W J H Penninx & W J G Hoogendijk

  3. Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands

    E C Verbeek & T Uithuisje

  4. EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands

    Y Milaneschi, J G Hugtenburg & B W J H Penninx

  5. Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

    Y Milaneschi, B W J H Penninx & W J G Hoogendijk

  6. European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, The Netherlands

    M R Bevova

  7. Genome Biology of Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Tübingen, Germany

    P Heutink

  8. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    B W J H Penninx

  9. Department of Psychiatry, University Medical Center Leiden, Leiden, The Netherlands

    B W J H Penninx

  10. Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands

    W J G Hoogendijk

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Bet, P., Verbeek, E., Milaneschi, Y. et al. A common polymorphism in the ABCB1 gene is associated with side effects of PGP-dependent antidepressants in a large naturalistic Dutch cohort. Pharmacogenomics J 16, 202–208 (2016). https://doi.org/10.1038/tpj.2015.38

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