Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS).
Adverse drug events
Clinical pharmacogenomics
Companion diagnostics
Cytochromes
DNA test
Diseases of the central nervous system
Dose adjustment
Drug metabolization
Precision medicine and personalized therapy
Psychiatry
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
15 04 2021
15 04 2021
Historique:
received:
12
01
2021
accepted:
02
04
2021
entrez:
16
4
2021
pubmed:
17
4
2021
medline:
15
5
2021
Statut:
epublish
Résumé
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. 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 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. Overall, results illustrate that the PGx-CNS panel is a valuable tool supporting therapeutic medical decisions, urging its broad clinical implementation.
Sections du résumé
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.
Identifiants
pubmed: 33858454
doi: 10.1186/s12967-021-02816-3
pii: 10.1186/s12967-021-02816-3
pmc: PMC8048316
doi:
Substances chimiques
Pharmaceutical Preparations
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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