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.
Highlights
Pharmacogenomics (PGx) aims to delineate individual differences in drug use, both in terms of efficacy and toxicity, with the underlying genetic profile [1]
Phase I included the analysis of 1,931 PGx variants in 231 pharmacogenes, using the Affymetrix DMETTM Plus platform, for 847 samples from 11 European populations, which were subsequently compared against 499 samples from the Saudi Arabian population and 106 samples from South African populations (Table 1)
The microattribution approach was implemented towards the assessment of the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes
Summary
Pharmacogenomics (PGx) aims to delineate individual differences in drug use, both in terms of efficacy and toxicity, with the underlying genetic profile [1]. There are significant geographic differences in the prevalence of several ADRs and medication efficacy [6,7]. This is not unexpected considering the fact that these differences in drug response are correlated with genomic variants, whose allelic frequencies vary among different population and racial groups. As with every genomic variant, PGx biomarkers that have been associated with both adverse events and variable drug efficacy have significant geographic variability, as far as their allelic frequencies are concerned
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