title: A common polymorphism in the ABCB1 gene is associated with side effects of PGP-dependent antidepressants in a large naturalistic Dutch cohort.
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.
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands.|Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Bet
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: E C
authors.initials: EC
authors.lastname: Verbeek
authors.affiliation: EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Milaneschi
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: D B M
authors.initials: DB
authors.lastname: Straver
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Uithuisje
authors.affiliation: European Research Institute for the Biology of Ageing, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: Bevova
authors.affiliation: Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, The Netherlands.|EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Hugtenburg
authors.affiliation: Genome Biology of Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Heutink
authors.affiliation: Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.|EMGO Institute, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Department of Psychiatry, University Medical Center Leiden, Leiden, The Netherlands.
authors.forename: B W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.|Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.|Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: W J G
authors.initials: WJ
authors.lastname: Hoogendijk
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000928:Antidepressive Agents; D065731:Cytochrome P-450 CYP2C19