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Polymorphic CYP2A6 and its clinical and toxicological significance

The Pharmacogenomics Journal volume 3, pages 6–7 (2003)Cite this article

The cytochrome P450 (CYP) enzymes play a crucial role in the metabolism of exogenous compounds including pharmaceutical agents. It is estimated that about one-half of drugs are primarily cleared from the body through the action of CYP enzymes mainly in the liver.1 About 40% of human CYP-dependent drug metabolism is carried out by polymorphic enzymes, which can result in therapeutic failures and adverse effects from ensuing interindividual variability in drug concentrations. Several examples exist where subjects carrying certain variant alleles suffer from adverse effects from drug treatment due to the presence of defective alleles.2 The well-known polymorphic CYP genes are CYP2C9, CYP2C19 and CYP2D6. Many of the polymorphic CYP enzymes also metabolize numerous toxicologically significant compounds, such as food additives, pollutants, solvents, and recreational drugs, many of which cause acute or delayed toxic effects.3

CYP2A6 represents up to 10% of human microsomal P450 proteins. CYP2A6 is the major enzyme catalysing the oxidative metabolism of nicotine and cotinine and it contributes to the metabolism of some pharmaceuticals (eg fadrozole, tegafur, SM-12502), nitrosamines, other carcinogens (eg aflatoxin B1) and a number of coumarin-type alkaloids.4,5,6 CYP2A6 may be inducible by antiepileptic drugs and it is decreased in alcohol-induced severe cirrhosis.4

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Acknowledgements

Thanks to Drs Olavi Pelkonen (University of Oulu, Finland) and Hannu Raunio (University of Kuopio, Finland) for constructive criticims.

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  1. Department of Pharmacology and Toxicology, University of Oulu, Finland

    A Rautio

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  1. A Rautio
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Correspondence to A Rautio.

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Rautio, A. Polymorphic CYP2A6 and its clinical and toxicological significance. Pharmacogenomics J 3, 6–7 (2003). https://doi.org/10.1038/sj.tpj.6500154

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