REVIEW article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1611203
This article is part of the Research TopicPharmacoepigenetics in Personalized MedicineView all articles
Epigenetics in pharmacogenes encoding metabolizing enzymes of second-generation antipsychotics used in schizophrenia and its clinical implications
Provisionally accepted
Angel T. Alvarado1*
Amparo Iris Zavaleta2César Li-Amenero3Maria R. Bendezú4Jorge A. Garcia4Haydee Chávez4
Juan J. Palomino-Jhong4Felipe Surco-Laos4Doris Laos-Anchante4Elizabeth J. Melgar-Merino4Mario Bolarte-Arteaga5Nesquen Tasayco-Yataco6Ricardo Pariona-Llanos7- 1International Research Unit in Molecular Pharmacology and Genomic Medicine (UNIPHARMOGEM), VRI, San Ignacio de Loyola University, Lima, Peru
- 2Laboratorio de Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima 01, Peru, Lima, Peru
- 3Victor Larco Herrera Hospital, Lima, Peru
- 4Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University of Ica, Ica, Peru., ICA, Peru
- 5Human Medicine, Continental University, Av. Alfredo Mendiola 5210, Los Olivos 15304, Peru., Lima, Peru
- 6Human Medicine, Faculty of Health Sciences, Norbert Wiener University,, Lima, Peru
- 7Peruvian University of Applied Sciences, Lima, Lima, Peru
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Schizophrenia is a neuropsychiatric disorder caused by neurochemical alterations, non-genetic, genetic, epigenetic and environmental factors. Pharmacoepigenetics studies the relationship between epigenetic variability and response to drugs. The objective was to realize a descriptive review of the current state of knowledge on epigenetic molecular mechanisms in pharmacogenes encoding metabolizing enzymes of second-generation antipsychotics drugs used in schizophrenia and their clinical implications. A brief description of the pharmacogenes CYP2D6, CYP1A2, CYP2C9, CYP2C19 and CYP3A4, enzymes and metabolism of second-generation antipsychotic drugs (SGAs) such as clozapine, olanzapine, risperidone, paliperidone and quetiapine was made. The central review was on the epigenetic molecular mechanisms of DNA methylation, histone methylation and acetylation of pharmacogenes, likewise, epigenetic changes due to enzyme-inducing drugs and SGAs, and their clinical implications, were described. Despite the limited scientific literature published on the epigenetics that regulate pharmacogenes, it has been shown that DNA methylation and histone trimethylation and acetylation are the main epigenetic mechanisms in pharmacogenes, alike, some enzyme-inducing drugs would promote epigenetic changes. This review has clinical implications for the medical-clinical care and treatment of schizophrenia.
Keywords: epigenetics, pharmacogenes, Schizophrenia, antipsychotic drugs, clinical implications
Received: 14 Apr 2025; Accepted: 25 Aug 2025.
Copyright: © 2025 Alvarado, Zavaleta, Li-Amenero, Bendezú, Garcia, Chávez, Palomino-Jhong, Surco-Laos, Laos-Anchante, Melgar-Merino, Bolarte-Arteaga, Tasayco-Yataco and Pariona-Llanos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Angel T. Alvarado, International Research Unit in Molecular Pharmacology and Genomic Medicine (UNIPHARMOGEM), VRI, San Ignacio de Loyola University, Lima, Peru
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.