Update: genetic polymorphism of drug metabolizing enzymes in humans

The cytochrome P450 (P450 or CYP) monooxygenases, CYP2D6, CYP2C19, CYP2E1 and CYP2C9, and non-P450 monooxygenases, N-acetyltransferase, thioprine methyltransferases and dihydropyrimidine dehydrogenase, all display polymorphism. CYP2D6 and CYP2C19 have been studied extensively and, despite their low abundance in the liver, they have been found to catalyse the metabolism of many drugs. CYP2D6 has many allelic variants, whereas CYP2C19 has only two. Most variants are translated into inactive, truncated proteins or fail to express protein. There is, as yet, no clear information about CYP2E1 polymorphism. In addition, genetic differences in certain foreign-compound metabolizing enzymes, such as Phase II enzymes, have been shown to be associated with an increased risk of developing environmentally and occupationally related diseases such as cancer. When two drugs that are substrates of a polymorphic CYP enzyme are administered concomitantly during drug therapy, each will compete for that enzyme and competitively inhibit the metabolism of the other substrate. This can result in toxicity. Patients who are poor metabolizers (PMs), extensive metabolizers (EMs) and ultrarapid metabolizers (URMs) can be identified. Having such information will help in determining the appropriate dosage of certain drugs when treating patients with an inherited abnormality of a drug-metabolizing enzyme. In view of the remarkable progress in this particular field, it is to be expected that more genetic polymorphisms will be discovered in the near future.