Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing
Background: The international drug agencies annotate pharmacogenes for many years. Pharmacogenetic testing is thus far only established in few settings, assuming that only few patients are actually affected by drug-gene interactions. Methods: 108 hospitalized patients with major depressive disorder...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Journal of Xenobiotics |
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| Online Access: | https://www.mdpi.com/2039-4713/12/4/22 |
| _version_ | 1797456874786783232 |
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| author | Sibylle Christine Roll Martina Hahn |
| author_facet | Sibylle Christine Roll Martina Hahn |
| author_sort | Sibylle Christine Roll |
| collection | DOAJ |
| description | Background: The international drug agencies annotate pharmacogenes for many years. Pharmacogenetic testing is thus far only established in few settings, assuming that only few patients are actually affected by drug-gene interactions. Methods: 108 hospitalized patients with major depressive disorder were genotyped for <i>CYP1A2</i>, <i>CYP2B6</i>, <i>CYP2C8</i>, <i>CYP2C9</i>, <i>CYP2C19</i>, <i>CYP2D6</i>, <i>CYP3A4</i>, <i>CYP3A5</i>, <i>NAT2</i>, <i>DPYD</i>; <i>VKORC1</i> and <i>TMTP</i>. Results: We found 583 (mean 5.4, median 5) divergent phenotypes (i.e., divergent from the common phenotypes considered normal, e.g., extensive metabolizer) in the 12 analyzed pharmacokinetic genes. The rate for at least one divergent phenotype was 100% in our cohort for CYP, but also for all 12 important pharmacogenes: patients had at least two divergent phenotypes. Compared to a large Danish cohort, CYP2C9 NM and IM status, CYP2C19 UM, CYP2D6 UM and DYPD (GAS 0, 1, 2) genotypes differed statistical significantly. For CYP2D6 and CYP2C19, 13% of the patients were normal metabolizers for both enzymes in our cohort, but this value was 27.3% in the Danish cohort, which is a highly significant difference (<i>p</i> < 0.0001). Conclusion: Divergent phenotypes in pharmacogenes are not the exception, but the rule. Patients with divergent phenotypes seem more prone for hospitalization, emphasizing the need for pre-emptive testing to avoid inefficacy and adverse drug effects in all patients. |
| first_indexed | 2024-03-09T16:14:04Z |
| format | Article |
| id | doaj.art-9669cc84be3846baa24a5018d02a361a |
| institution | Directory Open Access Journal |
| issn | 2039-4705 2039-4713 |
| language | English |
| last_indexed | 2024-03-09T16:14:04Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Xenobiotics |
| spelling | doaj.art-9669cc84be3846baa24a5018d02a361a2023-11-24T16:00:44ZengMDPI AGJournal of Xenobiotics2039-47052039-47132022-10-0112431732810.3390/jox12040022Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive TestingSibylle Christine Roll0Martina Hahn1Department of Mental Health, Varisano Hospital Frankfurt Höchst GmbH, Gotenstraße 6-8, 65929 Frankfurt, GermanyDepartment of Mental Health, Varisano Hospital Frankfurt Höchst GmbH, Gotenstraße 6-8, 65929 Frankfurt, GermanyBackground: The international drug agencies annotate pharmacogenes for many years. Pharmacogenetic testing is thus far only established in few settings, assuming that only few patients are actually affected by drug-gene interactions. Methods: 108 hospitalized patients with major depressive disorder were genotyped for <i>CYP1A2</i>, <i>CYP2B6</i>, <i>CYP2C8</i>, <i>CYP2C9</i>, <i>CYP2C19</i>, <i>CYP2D6</i>, <i>CYP3A4</i>, <i>CYP3A5</i>, <i>NAT2</i>, <i>DPYD</i>; <i>VKORC1</i> and <i>TMTP</i>. Results: We found 583 (mean 5.4, median 5) divergent phenotypes (i.e., divergent from the common phenotypes considered normal, e.g., extensive metabolizer) in the 12 analyzed pharmacokinetic genes. The rate for at least one divergent phenotype was 100% in our cohort for CYP, but also for all 12 important pharmacogenes: patients had at least two divergent phenotypes. Compared to a large Danish cohort, CYP2C9 NM and IM status, CYP2C19 UM, CYP2D6 UM and DYPD (GAS 0, 1, 2) genotypes differed statistical significantly. For CYP2D6 and CYP2C19, 13% of the patients were normal metabolizers for both enzymes in our cohort, but this value was 27.3% in the Danish cohort, which is a highly significant difference (<i>p</i> < 0.0001). Conclusion: Divergent phenotypes in pharmacogenes are not the exception, but the rule. Patients with divergent phenotypes seem more prone for hospitalization, emphasizing the need for pre-emptive testing to avoid inefficacy and adverse drug effects in all patients.https://www.mdpi.com/2039-4713/12/4/22divergent phenotypespharmacokineticspre-emptive testingpharmacogeneticsdrug-gene interactionpharmacogenes |
| spellingShingle | Sibylle Christine Roll Martina Hahn Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing Journal of Xenobiotics divergent phenotypes pharmacokinetics pre-emptive testing pharmacogenetics drug-gene interaction pharmacogenes |
| title | Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing |
| title_full | Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing |
| title_fullStr | Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing |
| title_full_unstemmed | Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing |
| title_short | Rates of Divergent Pharmacogenes in a Psychiatric Cohort of Inpatients with Depression—Arguments for Preemptive Testing |
| title_sort | rates of divergent pharmacogenes in a psychiatric cohort of inpatients with depression arguments for preemptive testing |
| topic | divergent phenotypes pharmacokinetics pre-emptive testing pharmacogenetics drug-gene interaction pharmacogenes |
| url | https://www.mdpi.com/2039-4713/12/4/22 |
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