PharmacogenomicsBMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7220.1286 (Published 13 November 1999) Cite this as: BMJ 1999;319:1286
- Wolfgang Sadée, professor ([email protected])
- Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California, San Francisco, CA94143-0446, USA
We all differ in our response to drug treatment—occasionally with dramatic effects The era of “one drug fits all patients” is about to give way to individualised therapy matching the patient's unique genetic make up with an optimally effective drug.1 Pharmacogenetics and pharmacogenomics are the emerging disciplines that are leading the way towards individualised medicine. 2 3 Initially, researchers focused their attention on pharmacogenetics—variations in single candidate genes responsible for variable drug response. Subsequently, studies involving the entire human genome broadened the scope of investigation, giving rise to pharmacogenomics as one of the “hottest” fields in biotechnology today.
Response to drug treatment can vary greatly between patients; genetic factors have a major role in treatment outcome
Pharmacogenetics and pharmacogenomics are emerging disciplines that focus on genetic determinants of drug response at the levels of single genes or the entire human genome respectively
Technologies involving gene chip arrays can determine thousands of variations in DNA sequences for individual patients; most variants are single nucleotide polymorphisms
Pharmacogenomics aims at establishing a signature of DNA sequence variants that are characteristic of individual patients to assess disease susceptibility and select the optimal drug treatment
This approach has the potential to revolutionise prevention and treatment of diseases
Unexpected drug reactions have been noted for some time, but the systematic study of hereditary origins began only in the 1950s. A few patients developed prolonged respiratory muscular paralysis after being given succinylcholine (suxamethonium), a short acting muscle relaxant widely used in surgery and electroshock treatment. In the 1970s, a trial with the antihypertensive agent debrisoquine resulted in a precipitous drop of blood pressure and collapse in nearly 10% of volunteers. Furthermore, isoniazid therapy for tuberculosis caused peripheral neuropathies in patients who were sensitive to the neurotoxic effects of the drug. Ground breaking genetic and biochemical studies …
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