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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Research

Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS)

Authors: E. Bothos, E. Ntoumou, K. Kelaidoni, D. Roukas, N. Drakoulis, M. Papasavva, F. A. Karakostis, P. Moulos, K. Karakostis

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

Pharmacogenomics describes the link between gene variations (polymorphisms) and drug responses. In view of the implementation of precision medicine in personalized healthcare, pharmacogenetic tests have recently been introduced in the clinical practice. However, the translational aspects of such tests have been limited due to the lack of robust population-based evidence.

Materials

In this paper we present a novel pharmacogenetic panel (iDNA Genomics-PGx–CNS or PGx–CNS), consisting of 24 single nucleotide polymorphisms (SNPs) on 13 genes involved in the signaling or/and the metabolism of 28 approved drugs currently administered to treat diseases of the Central Nervous System (CNS). We have tested the PGx–CNS panel on 501 patient-derived DNA samples from a southeastern European population and applied biostatistical analyses on the pharmacogenetic associations involving drug selection, dosing and the risk of adverse drug events (ADEs).

Results

Results reveal the occurrences of each SNP in the sample and a strong correlation with the European population. Nonlinear principal component analysis strongly indicates co-occurrences of certain variants. The metabolization efficiency (poor, intermediate, extensive, ultra-rapid) and the frequency of clinical useful pharmacogenetic, associations in the population (drug relevance), are also described, along with four exemplar clinical cases illustrating the strong potential of the PGx–CNS panel, as a companion diagnostic assay. It is noted that pharmacogenetic associations involving copy number variations (CNVs) or the HLA gene were not included in this analysis.

Conclusions

Overall, results illustrate that the PGx–CNS panel is a valuable tool supporting therapeutic medical decisions, urging its broad clinical implementation.
Appendix
Available only for authorised users
Footnotes
4
Medical classification as listed by WHO under the range—Mental, Behavioral and Neurodevelopmental disorders.
 
5
Medical classification as listed by WHO under the range—Mental, Behavioral and Neurodevelopmental disorders.
 
6
Medical classification as listed by WHO under the range—Mental, Behavioral and Neurodevelopmental disorders.
 
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Metadata
Title
Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS)
Authors
E. Bothos
E. Ntoumou
K. Kelaidoni
D. Roukas
N. Drakoulis
M. Papasavva
F. A. Karakostis
P. Moulos
K. Karakostis
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-02816-3

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