Journal Article

Genetic Polymorphism and Toxicology—With Emphasis on Cytochrome P450

Inger Johansson and Magnus Ingelman-Sundberg

in Toxicological Sciences

Volume 120, issue 1, pages 1-13
Published in print March 2011 | ISSN: 1096-6080
Published online December 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq374
Genetic Polymorphism and Toxicology—With Emphasis on Cytochrome P450

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Individual susceptibility to environmental, chemical, and drug toxicity is to some extent determined by polymorphism in drug-metabolizing enzymes, in particular the cytochromes P450 (CYPs). This polymorphism is in particular translated into risk differences concerning drugs metabolized by the highly polymorphic enzymes CYP2C9, CYP2C19, and CYP2D6, whereas CYP enzymes active in procarcinogen activation are relatively well conserved without important functional polymorphisms. Examples of drug toxicities that can be predicted by P450 polymorphism include those exerted by codeine, tramadol, warfarin, acenocoumarol, and clopidogrel. The polymorphic CYP2A6 has a role in nicotine metabolism and smoking behavior. Besides this genetic variation, genome-wide association studies now allow for the identification of an increasing number of predictive genetic biomarkers among, e.g., human leukocyte antigens and to some extent drug transporters that provide useful information regarding the choice of the drug and drug dosage in order to avoid toxicity. The translation of this information into the clinical practice has been slow; however, an increasing number of pharmacogenomic drug labels are assigned, where the predictive genotyping before drug treatment can be mandatory, recommended, or only for informational purposes. In this review, we provide an update of the field with emphasis on CYP polymorphism.

Keywords: adverse drug reactions; nicotine; clopidogrel; CYP2D6; CYP2C9; CYP2C19; warfarin; codeine

Journal Article.  6335 words. 

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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