E Bothos1,2, E Ntoumou3, K Kelaidoni3, D Roukas4, N Drakoulis5, M Papasavva5, F A Karakostis6, P Moulos1,7, K Karakostis8. 1. HybridStat Predictive Analytics, Athens, Greece. 2. Institute of Communications and Computer Systems, National Technical University of Athens, Athens, Greece. 3. iDNA Genomics Private Company, Evrota 25, Kifissia, 145 64, Athens, Greece. 4. Department of Psychiatry, Army Hospital (NIMTS), 417 Veterans, 115 21, Athens, Greece. 5. Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, 15771, Zografou, Greece. 6. Paleoanthropology, Senckenberg Centre for Human Evolution and Palaeoenvironment, Department of Geosciences, University of Tübingen, Tübingen, Germany. 7. Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center 'Alexander Fleming', 34 Fleming str, 16672, Athens, Vari, Greece. 8. iDNA Genomics Private Company, Evrota 25, Kifissia, 145 64, Athens, Greece. chem898@yahoo.gr.
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.
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.
Entities:
Keywords:
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
Authors: M Whirl-Carrillo; E M McDonagh; J M Hebert; L Gong; K Sangkuhl; C F Thorn; R B Altman; T E Klein Journal: Clin Pharmacol Ther Date: 2012-10 Impact factor: 6.875
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