Frequencies of Genetic Polymorphisms of Clinically Relevant Gene-Drug Pairs in a German Psychiatric Inpatient Population

Martina Hahn; Daniel J. Müller; Sibylle C. Roll

doi:10.1055/a-1312-7175

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2021; 54(02): 81-89
DOI: 10.1055/a-1312-7175

Original Paper

Frequencies of Genetic Polymorphisms of Clinically Relevant Gene-Drug Pairs in a German Psychiatric Inpatient Population

Authors

Martina Hahn

¹Vitos Klinik Eichberg, Eltville, Germany
Daniel J. Müller

²Campbell Family Mental Health Research Institute, Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health, Toronto, Canada

³Department of Psychiatry, University of Toronto, Toronto, ON, Canada
Sibylle C. Roll

¹Vitos Klinik Eichberg, Eltville, Germany

Abstract

Introduction Genetic variation is known to affect enzymatic activities allowing differentiating various metabolizer types (e. g., slow or rapid metabolizers), in particular CYP2C19 and CYP2D6.

Methods PGx-testing was conducted in adult major depressive disorder inpatients admitted to the Vitos Klinik Eichberg between 11/2016 and 7/2017 (n=108, 57% female). We conducted a two-sided Z-Test (p=0.05) to analyze and compare frequencies of CYP2D6, CYP2C19, CYP3A4, CYP3A5 and CYP2C9 metabolizer groups with other European and psychiatric inpatient cohorts. The HLA-A and –B genes were also analyzed.

Results Non-normal metabolizer status of CYP2D6 were present in 47%. More specifically, 35 % were intermediate, 7% poor and 4% ultra-rapid metabolizers. 68% were CYP2C19 non-normal metabolizers. 8% were ultra-rapid and 31% rapid metabolizers. Notably, only 13% were NM for CYP2C19 and NM for CYP2D6 (activity score of 1 or more). For CYP2C9 we found 16% to be intermediate metabolizers, 1.0% poor metabolizer. CYP3A4 and CYP3A5 genetic polymorphisms were present in 25% and 19% respectively. HLA-B TAG- SNPs for *15:01 was positive in 25 patients, showing the need for different Tag-SNPs in Caucasians. HLA-B *57:01 TAG-SNP was positive in 8% of the patients, HLA-A TAG-SNP for *31:01 in Caucasians was positive in 9%. Z-Test showed statistical significance for our results.

Discussion Our results suggest that our psychiatric inpatients were enriched with genotypes consistent with non-normal drug metabolism compared to reference populations. We therefore conclude that pharmacogenetic testing should be implemented in clinical practice to guide drug therapy.

Key words

Cytochrome P450 (CYP) enzymes - Pharmacogenetics - psychiatry - Antidepressants - personalized medicine

Full Text

References

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