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

Autor: Eva C. Verbeek, Witte J.G. Hoogendijk, Jacqueline G. Hugtenburg, T. Uithuisje, Peter Heutink, Marianna R. Bevova, Yuri Milaneschi, Brenda W.J.H. Penninx, D.B.M. Straver, Pierre M. Bet
Přispěvatelé: Psychiatry, Clinical pharmacology and pharmacy, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, EMGO - Mental health
Rok vydání: 2016
Předmět:
Male
LINKAGE DISEQUILIBRIUM
ABCB1 protein
human
Pharmacology
030226 pharmacology & pharmacy
Cohort Studies
0302 clinical medicine
Genotype
THERAPEUTIC RESPONSE
MAJOR DEPRESSIVE DISORDER
integumentary system
Middle Aged
Paroxetine
Antidepressive Agents
DRUG RESPONSE
CITALOPRAM
adverse effects [Antidepressive Agents]
Molecular Medicine
Major depressive disorder
Antidepressant
Female
medicine.drug
SEXUAL DYSFUNCTION
Adult
SEQUENCE VARIATIONS
ATP Binding Cassette Transporter
Subfamily B
Single-nucleotide polymorphism
MDR1
PAROXETINE
CYP2C19
Citalopram
genetics [ATP Binding Cassette Transporter
Subfamily B]
Polymorphism
Single Nucleotide
03 medical and health sciences
Genetics
medicine
SNP
Humans
ddc:610
Genetic Association Studies
genetics [Cytochrome P-450 CYP2C19]
business.industry
CLINICAL-RESPONSE
metabolism [ATP Binding Cassette Transporter
Subfamily B]
medicine.disease
030227 psychiatry
Cytochrome P-450 CYP2C19
business
Zdroj: Pharmacogenomics Journal, 16(2), 202-208. Nature Publishing Group
Bet, P M, Verbeek, E C, Milaneschi, Y, Straver, D B M, Uithuisje, T, Bevova, M R, Hugtenburg, J G, Heutink, P, Penninx, B W J H & Hoogendijk, W J G 2016, ' A common polymorphism in the ABCB1 gene is associated with side effects of PGP-dependent antidepressants in a large naturalistic Dutch cohort ', Pharmacogenomics Journal, vol. 16, no. 2, pp. 202-208 . https://doi.org/10.1038/tpj.2015.38
Pharmacogenomics journal, 16(2), 202-208. Nature Publishing Group
The pharmacogenomics journal 16(2), 202-208 (2015). doi:10.1038/tpj.2015.38
Pharmacogenomics Journal, 16(2), 202-208
ISSN: 1473-1150
1470-269X
DOI: 10.1038/tpj.2015.38
Popis: 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 x 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.
Databáze: OpenAIRE
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