A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countri...

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Main Authors:	Mizzi, Clint, Dalabira, Eleni, Kumuthini, Judit, Dzimiri, Nduna, Balogh, Istvan, Başak, Nazli, Böhm, Ruwen, Borg, Joseph, Borgiani, Paola, Bozina, Nada, Bruckmueller, Henrike, Burzynska, Beata, Carracedo, Angel, Cascorbi, Ingolf, Deltas, Constantinos, Dolzan, Vita, Fenech, Anthony, Grech, Godfrey, Kasiulevicius, Vytautas, Kádaši, Ľudevít, Kučinskas, Vaidutis, Khusnutdinova, Elza, Loukas, Yiannis L., Macek, Milan, Makukh, Halyna, Mathijssen, Ron, Mitropoulos, Konstantinos, Mitropoulou, Christina, Novelli, Giuseppe, Papantoni, Ioanna, Pavlovic, Sonja, Saglio, Giuseppe, Setric, Jadranka, Stojiljkovic, Maja, Stubbs, Andrew P., Squassina, Alessio, Torres, Maria, Turnovec, Marek, van Schaik, Ron H., Voskarides, Konstantinos, Wakil, Salma M., Werk, Anneke, del Zompo, Maria, Zukic, Branka, Katsila, Theodora, Lee, Ming Ta Michael, Motsinger-Rief, Alison, Mc Leod, Howard L., van der Spek, Peter J., Patrinos, George P.
Format:	Online
Language:	English
Published:	Public Library of Science 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026342/

id	pubmed-5026342
recordtype	oai_dc
spelling	pubmed-50263422016-09-27 A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics Mizzi, Clint Dalabira, Eleni Kumuthini, Judit Dzimiri, Nduna Balogh, Istvan Başak, Nazli Böhm, Ruwen Borg, Joseph Borgiani, Paola Bozina, Nada Bruckmueller, Henrike Burzynska, Beata Carracedo, Angel Cascorbi, Ingolf Deltas, Constantinos Dolzan, Vita Fenech, Anthony Grech, Godfrey Kasiulevicius, Vytautas Kádaši, Ľudevít Kučinskas, Vaidutis Khusnutdinova, Elza Loukas, Yiannis L. Macek, Milan Makukh, Halyna Mathijssen, Ron Mitropoulos, Konstantinos Mitropoulou, Christina Novelli, Giuseppe Papantoni, Ioanna Pavlovic, Sonja Saglio, Giuseppe Setric, Jadranka Stojiljkovic, Maja Stubbs, Andrew P. Squassina, Alessio Torres, Maria Turnovec, Marek van Schaik, Ron H. Voskarides, Konstantinos Wakil, Salma M. Werk, Anneke del Zompo, Maria Zukic, Branka Katsila, Theodora Lee, Ming Ta Michael Motsinger-Rief, Alison Mc Leod, Howard L. van der Spek, Peter J. Patrinos, George P. Research Article Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant inter-population pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective. Public Library of Science 2016-09-16 /pmc/articles/PMC5026342/ /pubmed/27636550 http://dx.doi.org/10.1371/journal.pone.0162866 Text en © 2016 Mizzi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Mizzi, Clint Dalabira, Eleni Kumuthini, Judit Dzimiri, Nduna Balogh, Istvan Başak, Nazli Böhm, Ruwen Borg, Joseph Borgiani, Paola Bozina, Nada Bruckmueller, Henrike Burzynska, Beata Carracedo, Angel Cascorbi, Ingolf Deltas, Constantinos Dolzan, Vita Fenech, Anthony Grech, Godfrey Kasiulevicius, Vytautas Kádaši, Ľudevít Kučinskas, Vaidutis Khusnutdinova, Elza Loukas, Yiannis L. Macek, Milan Makukh, Halyna Mathijssen, Ron Mitropoulos, Konstantinos Mitropoulou, Christina Novelli, Giuseppe Papantoni, Ioanna Pavlovic, Sonja Saglio, Giuseppe Setric, Jadranka Stojiljkovic, Maja Stubbs, Andrew P. Squassina, Alessio Torres, Maria Turnovec, Marek van Schaik, Ron H. Voskarides, Konstantinos Wakil, Salma M. Werk, Anneke del Zompo, Maria Zukic, Branka Katsila, Theodora Lee, Ming Ta Michael Motsinger-Rief, Alison Mc Leod, Howard L. van der Spek, Peter J. Patrinos, George P.
spellingShingle	Mizzi, Clint Dalabira, Eleni Kumuthini, Judit Dzimiri, Nduna Balogh, Istvan Başak, Nazli Böhm, Ruwen Borg, Joseph Borgiani, Paola Bozina, Nada Bruckmueller, Henrike Burzynska, Beata Carracedo, Angel Cascorbi, Ingolf Deltas, Constantinos Dolzan, Vita Fenech, Anthony Grech, Godfrey Kasiulevicius, Vytautas Kádaši, Ľudevít Kučinskas, Vaidutis Khusnutdinova, Elza Loukas, Yiannis L. Macek, Milan Makukh, Halyna Mathijssen, Ron Mitropoulos, Konstantinos Mitropoulou, Christina Novelli, Giuseppe Papantoni, Ioanna Pavlovic, Sonja Saglio, Giuseppe Setric, Jadranka Stojiljkovic, Maja Stubbs, Andrew P. Squassina, Alessio Torres, Maria Turnovec, Marek van Schaik, Ron H. Voskarides, Konstantinos Wakil, Salma M. Werk, Anneke del Zompo, Maria Zukic, Branka Katsila, Theodora Lee, Ming Ta Michael Motsinger-Rief, Alison Mc Leod, Howard L. van der Spek, Peter J. Patrinos, George P. A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics
author_facet	Mizzi, Clint Dalabira, Eleni Kumuthini, Judit Dzimiri, Nduna Balogh, Istvan Başak, Nazli Böhm, Ruwen Borg, Joseph Borgiani, Paola Bozina, Nada Bruckmueller, Henrike Burzynska, Beata Carracedo, Angel Cascorbi, Ingolf Deltas, Constantinos Dolzan, Vita Fenech, Anthony Grech, Godfrey Kasiulevicius, Vytautas Kádaši, Ľudevít Kučinskas, Vaidutis Khusnutdinova, Elza Loukas, Yiannis L. Macek, Milan Makukh, Halyna Mathijssen, Ron Mitropoulos, Konstantinos Mitropoulou, Christina Novelli, Giuseppe Papantoni, Ioanna Pavlovic, Sonja Saglio, Giuseppe Setric, Jadranka Stojiljkovic, Maja Stubbs, Andrew P. Squassina, Alessio Torres, Maria Turnovec, Marek van Schaik, Ron H. Voskarides, Konstantinos Wakil, Salma M. Werk, Anneke del Zompo, Maria Zukic, Branka Katsila, Theodora Lee, Ming Ta Michael Motsinger-Rief, Alison Mc Leod, Howard L. van der Spek, Peter J. Patrinos, George P.
author_sort	Mizzi, Clint
title	A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics
title_short	A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics
title_full	A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics
title_fullStr	A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics
title_full_unstemmed	A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics
title_sort	european spectrum of pharmacogenomic biomarkers: implications for clinical pharmacogenomics
description	Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant inter-population pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective.
publisher	Public Library of Science
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026342/
_version_	1613653936596582400

A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics

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