Issue: 2013 > April > special article

A clinical approach to pharmacogenetics

L.C.G. de Graaff, R.H.N. van Schaik, T. van Gelder


Taking into account the high frequency of adverse drug
reactions (ADRs) in the clinic and taking into account the
growing knowledge of the genetic mechanisms underlying
some of these ADRs, we believe that every clinician should
know at least the basic principles of pharmacogenetics.
However, our experience is that many clinicians are
unaware of the potential contribution of pharmacogenetic
testing and have not implemented this new modality in
their daily practice. We present a case of Stevens-Johnson syndrome in a patient treated with carbamazepine. Following the pathways of clinical reasoning, we describe the possibilities of pharmacogenetic testing in the clinic (HLA-B*1502 and HLA-A*3101 in our patient). We describe the pharmacological and pharmacogenetic aspects relevant for the clinician’s daily practice (the existence of ADR subtypes, cytochrome P450, drug-drug interactions, genetic variations, CYP450 and HLA genotyping). Based on the Dutch top 100 of most prescribed drugs, we provide data on CYP450 and HLA genotypes relevant to those 100 most commonly used drugs. We discuss the availability and costs of pharmacogenetic testing, show a calculation of the ‘number needed to genotype’ and, based on these
data, we propose a decision model for pharmacogenetic
testing by clinicians.