President & CEO: African Institute of Biomedical Science and Technology (AiBST Distinguished Professor: University of the Witwatersrand – Director: Consortium for Genomics and Therapeutics in Africa (CGTA)
Pharmacogenomics in Personalized Medicine – from research bench to patient bedside in Africa
Host: L. Donaldson
Pharmacogenomics (PGx) evaluates drug-gene interactions (DGI) that affect drug safety and efficacy. Research has uncovered numerous variations in genes that code for drug targets and for processes that affect drug metabolizing enzymes & transporters, that have been shown to affect the pharmacodynamics (PD) or the pharmacokinetics (PK) of some medicines. Mechanistic and clinical studies have gone on to show that some of these effects can have a profound effect on treatment outcomes. Most of this work has been done in people of European ancestry. The relatively few studies done in people of African ancestry, are however, revealing important observations; that whole genome sequence and variation in pharmacogenes among African populations is much higher than in Caucasians and Asians and that for clinically relevant pharmacogenes African populations have either unique variants or significantly different population frequencies compared to Caucasian and Asians. At a clinical level, observations of differential response with respect to efficacy and safety of some medicines in African patients compared to Caucasian patients have been made. The WHO pharmacovigilance database, Vigibase, shows that for most drugs, African populations have higher ADRs incidences than other world populations.
In response to this gap in basic and clinical PGx knowledge, over the past twenty five years my group has been working on discovering genetic variants associated with pharmacogenes and exploring drug-gene interactions potentially important for people of African Ancestry. This work has culminated in the design and analytical validation of a pharmacogenetic testing open array, GenoPharmR, that can predict clinical response for many medicines on the market. In this presentation I will present our journey from research lab work to patient bedside implementation studies that are likely to profoundly change the standard-of-care from one treatment fits all or generalisation of findings from one population to another to an approach that is individualised at personal and population level. Examples of drug-gene interactions involving CYP2B6- efavirenz, CYP2D6-tamoxifen, CYP2C19-clopidogrel, DPYD-5FU, and others will be covered.
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