Actionable Pharmacogenetic Variation in the Slovenian Genomic Database
Keli Hočevar1, Aleš Maver1, Borut Peterlin1
1Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Frontiers in Pharmacology
|April 2, 2019
Summary
Genetic variability in pharmacogenes impacts drug response. This study analyzed Slovenian exome data, revealing numerous actionable pharmacogenetic variants, including novel ones, for personalized medicine.
Area of Science:
- Genomics
- Pharmacogenetics
- Clinical Medicine
Background:
- Genetic variations in pharmacogenes influence drug efficacy and safety.
- Next-generation sequencing facilitates pharmacogene genotyping for personalized treatment.
- Understanding population-specific pharmacogenetic profiles is crucial.
Purpose of the Study:
- To determine the frequency and types of actionable pharmacogenetic findings in the Slovenian population.
- To assess the potential clinical utility of identified pharmacogenetic variants for personalized therapy.
- To provide a comprehensive overview of pharmacogenetic variants in Slovenia.
Main Methods:
- Analysis of de-identified exome sequencing data from 1904 Slovenian individuals.
- Investigation of variants in 293 drug response-associated genes.
- Classification of variants using population frequency, functional impact, pathogenicity predictions, PharmGKB, and ClinVar.
Main Results:
- Identified 24 known actionable pharmacogenetic variants (PharmGKB 1A/1B) affecting ~26 drugs, with 12 being rare (<1% frequency).
- Detected 61 additional variants with PharmGKB 2A/2B clinical annotations.
- Discovered 308 novel/rare potentially actionable variants, including 177 protein-truncating and 131 predicted pathogenic missense variants.
Conclusions:
- This study estimates the burden of pharmacogenetic variants in Slovenian exome data.
- The findings highlight the potential clinical usefulness of identified variants for personalized treatment strategies.
- A significant proportion of novel/rare variants were identified, offering new insights into drug response variability in the Slovenian population.
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