RESUMO
[This corrects the article DOI: 10.1371/journal.pone.0162866.].
RESUMO
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.
Assuntos
Marcadores Genéticos , Farmacogenética , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Análise por Conglomerados , Citocromo P-450 CYP2C9/genética , Etnicidade/genética , Europa (Continente) , Humanos , Vitamina K Epóxido Redutases/genética , Varfarina/administração & dosagem , Varfarina/farmacocinéticaRESUMO
BACKGROUND/AIMS: Pharmacogenomics aims to rationalize drug use by minimizing drug toxicity and/or by increasing drug efficacy. A large number of genomic markers have been correlated with variable drug responses and severity of adverse drug reactions. Although a number of these drugs bear pharmacogenomic information in their labels--approved by regulatory agencies--and comprehensive drug/gene lists exist online, information related to the respective pharmacogenomic biomarkers is currently missing from such lists. METHODS: We extracted information from the published literature and online resources and developed DruGeVar (http://drugevar.genomicmedicinealliance.org), an online resource triangulating drugs with genes and pharmacogenomic biomarkers in an effort to build a comprehensive database that could serve clinical pharmacogenomics. RESULTS AND CONCLUSIONS: A user-friendly data querying and visualization interface allows users to formulate simple and complex queries. Such a database would be readily applicable as a stand-alone resource or a plug-in module for other databases.
