05.02.1 Enzymes

The example of a polymorphism in an enzyme is with CYP2D6. About 15-25% of all drugs are substrates for this enzyme. For instance, haloperidol is metabolised by CYP2D6. With polymorphisms of CYP2D6 gene, 5-10% of people have slow metabolism of these drugs. The people who are slow metabolisers are likely to have higher plasma levels of drugs metabolised by CYP2D6, and more likely to have toxic effects. Thus, toxicity to haloperidol (e.g. tardive dyskinesia) is likely to be more common in slow metabolisers.

With some forms of the polymorphism, the people do not metabolise the drugs normally metabolised by this enzyme. For instance, the conversion of codeine to morphine, which is responsible for the analgesic effect of codeine, requires CYP2D6. Polymorphism in CYP2D6 leads to 10% of Caucasians not being able to convert codeine to morphine. In these 10%, there is a lack of efficacy of codeine, i.e. it does not have a sufficient analgesic effect.