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Verfasst von:Li, Danyang [VerfasserIn]   i
 Pain, Oliver [VerfasserIn]   i
 Fabbri, Chiara [VerfasserIn]   i
 Wong, Win Lee Edwin [VerfasserIn]   i
 Lo, Chris Wai Hang [VerfasserIn]   i
 Ripke, Stephan [VerfasserIn]   i
 Cattaneo, Annamaria [VerfasserIn]   i
 Souery, Daniel [VerfasserIn]   i
 Dernovsek, Mojca Z. [VerfasserIn]   i
 Henigsberg, Neven [VerfasserIn]   i
 Hauser, Joanna [VerfasserIn]   i
 Lewis, Glyn [VerfasserIn]   i
 Mors, Ole [VerfasserIn]   i
 Perroud, Nader [VerfasserIn]   i
 Rietschel, Marcella [VerfasserIn]   i
 Uher, Rudolf [VerfasserIn]   i
 Maier, Wolfgang [VerfasserIn]   i
 Baune, Bernhard T. [VerfasserIn]   i
 Biernacka, Joanna [VerfasserIn]   i
 Bondolfi, Guido [VerfasserIn]   i
 Domschke, Katharina [VerfasserIn]   i
 Kato, Masaki [VerfasserIn]   i
 Liu, Yu-Li [VerfasserIn]   i
 Serretti, Alessandro [VerfasserIn]   i
 Tsai, Shih-Jen [VerfasserIn]   i
 Weinshilboum, Richard [VerfasserIn]   i
 McIntosh, Andrew M. [VerfasserIn]   i
 Lewis, Cathryn M. [VerfasserIn]   i
Titel:Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation
Titelzusatz:a meta-analysis
Verf.angabe:Danyang Li, Oliver Pain, Chiara Fabbri, Win Lee Edwin Wong, Chris Wai Hang Lo, Stephan Ripke, Annamaria Cattaneo, Daniel Souery, Mojca Z. Dernovsek, Neven Henigsberg, Joanna Hauser, Glyn Lewis, Ole Mors, Nader Perroud, Marcella Rietschel, Rudolf Uher, Wolfgang Maier, Bernhard T. Baune, Joanna M. Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Richard Weinshilboum, the GSRD Consortium, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Andrew M. McIntosh and Cathryn M. Lewis
E-Jahr:2024
Jahr:19 July 2024
Umfang:8 S.
Fussnoten:Gesehen am 03.03.2025
Titel Quelle:Enthalten in: Translational Psychiatry
Ort Quelle:London : Nature Publishing Group, 2011
Jahr Quelle:2024
Band/Heft Quelle:14(2024), Artikel-ID 296, Seite 1-8
ISSN Quelle:2158-3188
Abstract:Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I2 = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.
DOI:doi:10.1038/s41398-024-02981-1
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1038/s41398-024-02981-1
 kostenfrei: Volltext: http://www.nature.com/articles/s41398-024-02981-1
 DOI: https://doi.org/10.1038/s41398-024-02981-1
Datenträger:Online-Ressource
Sprache:eng
Bibliogr. Hinweis:Errata: Li, Danyang: Correction: Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation
Sach-SW:Depression
 Predictive markers
K10plus-PPN:1918892083
Verknüpfungen:→ Zeitschrift

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