ABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0162866.].
ABSTRACT
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.
Subject(s)
Genetic Markers , Pharmacogenetics , Anticoagulants/administration & dosage , Anticoagulants/pharmacokinetics , Cluster Analysis , Cytochrome P-450 CYP2C9/genetics , Ethnicity/genetics , Europe , Humans , Vitamin K Epoxide Reductases/genetics , Warfarin/administration & dosage , Warfarin/pharmacokineticsABSTRACT
Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of "pharmacometabolomics-aided pharmacogenomics" in autoimmune diseases. We envisage merging pharmacometabolomic and pharmacogenomic data (to address the interplay of genomic and environmental influences) with information technologies to facilitate data analysis as well as sense- and decision-making on the basis of synergy between artificial and human intelligence. Humans can detect patterns, which computer algorithms may fail to do so, whereas data-intensive and cognitively complex settings and processes limit human ability. We propose that better-informed, rapid and cost-effective omics studies need the implementation of holistic and multidisciplinary approaches.
Subject(s)
Autoimmune Diseases/drug therapy , Autoimmune Diseases/genetics , Medical Informatics , Metabolomics , Algorithms , Autoimmune Diseases/metabolism , Autoimmune Diseases/pathology , Decision Making, Computer-Assisted , Drug Therapy, Computer-Assisted , Gene-Environment Interaction , Humans , Pharmacogenetics , Precision MedicineABSTRACT
Individual genetic composition is an important cause of variations in the response and tolerance to drug treatment. Pharmacogenomics is a modern discipline aiming to delineate individual genomic profiles and drug response. To date, there are several medical disciplines where pharmacogenomics is readily applicable, while in others its usefulness is yet to be demonstrated. Recent experimental evidence suggest that besides genomic variation within the human ß-globin gene cluster, other variants in modifier genes residing outside the human ß-globin gene cluster are significantly associated with response to hydroxyurea treatment in ß-type hemoglobinopathies patients, deducted from the increase in fetal hemoglobin levels. This article aims to provide an update and to discuss future challenges on the application of pharmacogenomics for ß-type hemoglobinopathies therapeutics in relation to the current pharmacological treatment modalities for those disorders.
