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British Medical Bulletin 55:366-386 (1999)
© 1999 The British Council

research-article

Pharmacogenetics

C Roland Wolf*, and Gillian Smith{dagger}

*Imperial Cancer Research Fund, Molecular Pharmacology Unit
{dagger}Biomedical Research Centre, Ninewells Hospital and Medical School Dundee, UK

Correspondence to: Prof C Roland Wolf, Imperial Cancer Research Fund, Molecular Pharmacology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK

Abstract

Inter-individual variability in drug response is a major clinical problem. Adverse drug reactions (ADRs) are common, are responsible for a number of debilitating side effects following drug therapy and are a significant cause of death. It is now clear that much of the observed variablity in durg response has a genetic basis, arising as a result of genetically-determined differences in durg absorption, disposition, metabolism or excretion. The best characterised pharmacogenetic polymorphisms are tohse within the phase I cytochrome P450 family of durg metabolising enzymes. One of these enzymes, CYP2D6 (debrisoquine hydroxlyase), metabolises one-quarter of all prescreibed drugs and is inactive in 6% of the Caucasian population. Individuals at risk of developing ADRs as a result of genetically-determined variation in genes such as CYP2D6 can now be identified using DNA-based tests. A detailed knowledge of the genetic basis of individual drug response is potentially of major clinical and economic importance and could provide the basis for a rational approach to drug prescription. This would have significant benefits for human health.


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