Oral Presentation Australian Society for Medical Research Annual Scientific Meeting 2016

Clinically actionable pharmacogenomic variants and medication exposure among community - dwelling older Australians (#33)

Nilofar Daneshi 1 , Elizabeth Holliday 2 3 , Stephen Hancock 2 3 , Jennifer Schneider 1 , John Attia 2 3 , Rodney Scott 1 4 , Liz Milward 1
  1. School of Biomedical Sciences and Pharmacy, The University of Newcastle, Newcastle, NSW, Australia
  2. Clinical Research Design, IT and Statistical Support (CReDITSS) Unit, Hunter Medical Research Institute, Newcastle, NSW, Australia
  3. Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health,Faculty of Health, University of Newcastle, Newsatle, NSW, Australia
  4. Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia

Rationale: Pre-emptive, panel-based genotyping simultaneously analyses gene variants of clinical relevance prior to medication exposure. This can potentially enhance outcomes for patients, physicians and the healthcare system.

Objective: To assess the prevalence of clinically actionable genotypes for six genes important in responses to five widely used drugs, in community dwelling older Australians participating in the Hunter cohort community study (Newcastle, Australia).

Methods and Results: Clinically actionable variants for 2122 participants (55 years and above) relevant to clopidogrel (CYP2C19 rs4244285), simvastatin (SLCO1B1 rs4149056), warfarin (CYP2C9 rs1057910, rs1799853 and VKORC1 rs9923231), thiopurines (TPMT rs1800460, rs1142345) and tacrolimus (CYP3A5 rs776746) were determined from Affymetrix Kaiser Axiom arrays or imputed from the HapMap Phase II European and 1000 Genomes reference panels. Actionable or high risk genotypes were assigned according to the guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC). At least 74% of participants (95% CI 72% - 76%) had strong level evidence for at least one medium- or high-risk actionable genotype that would trigger a change in standard therapy under current international recommendations. About 14% of these (95% CI 12% - 16%) were taking medication potentially affected by the genotype in question. Furthermore ~2.6% of all participants with medication data (95% CI 1.4% - 3.8%) had a high-risk clinically actionable genotype for a medication to which they were exposed.

Conclusion. Our analysis has revealed that the majority of people in this elderly community cohort have at least one clinically actionable pharmacogenotype that, based on CPIC guidelines, would trigger a change in standard therapy. The opportunities for drug-gene interactions were surprisingly common with over 10% of the cohort having strongly evidenced actionable genotypes also being exposed to risk associated medications. High-throughput pre-emptive genotyping before medication exposure can potentially improve medication safety and efficacy for older Australians.