Science, medicine, and the future

Pharmacogenetics

BMJ 2000; 320 doi: http://dx.doi.org/10.1136/bmj.320.7240.987 (Published 8 April 2000)
Cite this as: BMJ 2000;320:987

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  1. C Roland Wolf, director (rooney@icrf.icnet.uk)a,
  2. Gillian Smith, research associateb,
  3. Robert L Smithc
  1. a Imperial Cancer Research Fund Molecular Pharmacology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY
  2. b Biomedical Research Centre, Ninewells Hospital and Medical School, Dundee
  3. c Imperial College School of Medicine, Division of Biomedical Sciences, Section of Molecular Toxicology, Sir Alexander Fleming Building, London SW7 2AZ
  1. Correspondence to: C R Wolf

    Individual variation in response to drugs is a substantial clinical problem. Such variation ranges from failure to respond to a drug to adverse drug reactions and drug-drug interactions when several drugs are taken concomitantly. The clinical consequences range from patient discomfort through serious clinical illness to the occasional fatality. One UK study has suggested that about 1 in 15 hospital admissions are due to adverse drug reactions,1 and a recent US study estimated that 106 000 patients die and 2.2 million are injured each year by adverse reactions to prescribed drugs.2

    It is now clear that much individuality in drug response is inherited: this genetically determined variability in drug response defines the research area known as pharmacogenetics.3 This article discusses the potential of pharmacogenetic testing to improve both the efficacy and safety of drug prescribing.

    Methods

    We compiled the article from the published literature, information presented at scientific meetings, our own published research work, and information gained from working with the pharmaceutical industry on drugs in development.

    The human genome and polymorphism

    Pharmacogenetic research has gained enormous momentum, with recent advances in molecular genetics and genome sequencing. This is due to the emergence of technologies that permit rapid screening for specific polymorphisms, as well as our recently gained knowledge of the genetic sequences of target genes such as those coding for enzymes, ion channels, and other types of receptors involved in drug response.4

    Research in pharmacogenetics is currently developing in two main directions: firstly, identifying specific genes and gene products associated with various diseases, which may act as targets for new drugs, and, secondly, identifying genes and allelic variants of genes that affect our response to current drugs.

    Predicted developments

    Establishment of prescribing guidelines, based on clinical studies, for drugs that are subject to substantial polymorphic metabolism

    Prescribing advice will relate dose to genotype …

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