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A European Spectrum of Pharmacogenomic Biomarkers: Implications for Clinical Pharmacogenomics

C. Mizzi, E. Dalabira, J. Kumuthini, N. Dzimiri, I. Balogh, N. Başak, R. Böhm, J. Borg, P. Borgiani, N. Bozina, H. Bruckmueller, B. Burzynska, A. Carracedo, I. Cascorbi, C. Deltas, V. Dolzan, A. Fenech, G. Grech, V. Kasiulevicius, Ľ. Kádaši, V....

. 2016 ; 11 (9) : e0162866. [pub] 20160916

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc17031427

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.

Boğaziçi University Istanbul Turkey

Center for Proteomic and Genomic Research Observatory Cape Town South Africa

Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Comenius University Faculty of Natural Sciences Bratislava Slovakia Center for Molecular Medicine Slovak Academy of Sciences Bratislava Slovakia

Department of Human and Medical Genetics Faculty of Medicine Vilnius University Vilnius Lithuania

Erasmus University Medical Center Department of Clinical Chemistry Rotterdam the Netherlands

Erasmus University Medical Center Faculty of Medicine Department of Bioinformatics Rotterdam the Netherlands

Erasmus University Medical Center Faculty of Medicine Department of Bioinformatics Rotterdam the Netherlands University of Malta Faculty of Medicine and Surgery Department of Physiology and Biochemistry Msida Malta

Erasmus University Medical Center Faculty of Medicine Department of Bioinformatics Rotterdam the Netherlands University of Patras School of Health Sciences Department of Pharmacy Patras Greece

Institute of Biochemistry and Biophysics Polish Academy of Sciences Warsaw Poland

Institute of Biochemistry and Genetics Ufa Scientific Center Russian Academy of Sciences Ufa Russia Department of Genetics and Fundamental Medicine Bashkir State University Ufa Russia

Institute of Hereditary Pathology Ukrainian National Academy of Medical Sciences Lviv Ukraine

Institute of Molecular Genetics and Genetic Engineering University of Belgrade Laboratory of Molecular Biomedicine Belgrade Serbia

King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia

Moffitt Cancer Center Tampa FL United States of America

North Carolina State University Department of Statistics Raleigh NC United States of America

RIKEN Institute Center for Genomic Medicine Laboratory for International Alliance Yokohama Japan

The Golden Helix Foundation London United Kingdom

University Hospital Centre Zagreb Croatia

University Hospital Centre Zagreb Croatia University of Zagreb School of Medicine Zagreb Croatia

University of Athens Faculty of Pharmacy Department of Pharmaceutical Chemistry Athens Greece

University of Cagliari Department of Biomedical Sciences Cagliari Italy

University of Cyprus Molecular Medicine Research Center Department of Biological Sciences Nicosia Cyprus

University of Debrecen Debrecen Hungary

University of Kiel Institute for Experimental and Clinical Pharmacology Kiel Germany

University of Ljubljana Faculty of Medicine Ljubljana Slovenia

University of Malta Department of Applied Biomedical Science Faculty of Health Sciences Msida Malta

University of Malta Faculty of Medicine Department of Surgery Msida Malta

University of Patras School of Health Sciences Department of Pharmacy Patras Greece

University of Rome Tor Vergata Department of Biomedicine and Prevention Rome Italy

University of Santiago de Compostela Santiago Spain

University of Turin School of Medicine Turin Italy

Citace poskytuje Crossref.org

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