CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients
Abstract Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The p...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-45752-6 |
| _version_ | 1797647361360527360 |
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| author | Ferenc Fekete Ádám Menus Katalin Tóth Ádám Ferenc Kiss Annamária Minus Dávid Sirok Aleš Belič Ádám Póti Gábor Csukly Katalin Monostory |
| author_facet | Ferenc Fekete Ádám Menus Katalin Tóth Ádám Ferenc Kiss Annamária Minus Dávid Sirok Aleš Belič Ádám Póti Gábor Csukly Katalin Monostory |
| author_sort | Ferenc Fekete |
| collection | DOAJ |
| description | Abstract Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of − 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying − 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients’ olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients’ olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage. |
| first_indexed | 2024-03-11T15:15:10Z |
| format | Article |
| id | doaj.art-d3f79efa0bc240f7b6e998fc25c1e336 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T15:15:10Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-d3f79efa0bc240f7b6e998fc25c1e3362023-10-29T12:22:36ZengNature PortfolioScientific Reports2045-23222023-10-0113111310.1038/s41598-023-45752-6CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patientsFerenc Fekete0Ádám Menus1Katalin Tóth2Ádám Ferenc Kiss3Annamária Minus4Dávid Sirok5Aleš Belič6Ádám Póti7Gábor Csukly8Katalin Monostory9Institute of Enzymology, HUN-REN Research Centre for Natural SciencesDepartment of Psychiatry and Psychotherapy, Semmelweis UniversityInstitute of Enzymology, HUN-REN Research Centre for Natural SciencesInstitute of Enzymology, HUN-REN Research Centre for Natural SciencesInstitute of Enzymology, HUN-REN Research Centre for Natural SciencesInstitute of Enzymology, HUN-REN Research Centre for Natural SciencesLek Pharmaceuticals d.d.Institute of Enzymology, HUN-REN Research Centre for Natural SciencesDepartment of Psychiatry and Psychotherapy, Semmelweis UniversityInstitute of Enzymology, HUN-REN Research Centre for Natural SciencesAbstract Olanzapine is a commonly prescribed atypical antipsychotic agent for treatment of patients with schizophrenia and bipolar disorders. Previous in vitro studies using human liver microsomes identified CYP1A2 and CYP2D6 enzymes being responsible for CYP-mediated metabolism of olanzapine. The present work focused on the impact of CYP1A2 and CYP2D6 genetic polymorphisms as well as of CYP1A2 metabolizing capacity influenced by non-genetic factors (sex, age, smoking) on olanzapine blood concentration in patients with psychiatric disorders (N = 139). CYP2D6 genotype-based phenotype appeared to have negligible contribution to olanzapine metabolism, whereas a dominant role of CYP1A2 in olanzapine exposure was confirmed. However, CYP1A2 expression rather than CYP1A2 genetic variability was demonstrated to be associated with olanzapine concentration in patients. Significant contribution of − 163C > A (rs762551), the most common SNP (single nucleotide polymorphism) in CYP1A2 gene, to enhanced inducibility was confirmed by an increase in CYP1A2 mRNA expression in smokers carrying − 163A, and smoking was found to have appreciable impact on olanzapine concentration normalized by the dose/bodyweight. Furthermore, patients’ olanzapine exposure was in strong association with CYP1A2 expression; therefore, assaying CYP1A2 mRNA level in leukocytes can be an appropriate tool for the estimation of patients’ olanzapine metabolizing capacity and may be relevant in optimizing olanzapine dosage.https://doi.org/10.1038/s41598-023-45752-6 |
| spellingShingle | Ferenc Fekete Ádám Menus Katalin Tóth Ádám Ferenc Kiss Annamária Minus Dávid Sirok Aleš Belič Ádám Póti Gábor Csukly Katalin Monostory CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients Scientific Reports |
| title | CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients |
| title_full | CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients |
| title_fullStr | CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients |
| title_full_unstemmed | CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients |
| title_short | CYP1A2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients |
| title_sort | cyp1a2 expression rather than genotype is associated with olanzapine concentration in psychiatric patients |
| url | https://doi.org/10.1038/s41598-023-45752-6 |
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