Pharmacogenetics and the treatment of cardiovascular disease

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Abstract
The idea that the dose of a drug should be adjusted according to the patient's genotype is not new. It is well recognised that polymorphism in genes encoding P450 enzymes, N-acetyltransferase, and other key enzymes of drug metabolism are responsible for major inter-individual differences in blood concentrations of certain drugs. Clinically, poor metabolisers may be slow to activate and respond inadequately to some pro-drugs, or exhibit reduced clearance and increased effects from some pharmacologically active agents, particularly when the latter have a steep dose-response curve or a narrow therapeutic index. For example, the principle route of metabolism of flecainide and propafenone is via cytochrome P450 2D6 and multiple alleles have been identified that impair the activity of the enzyme. Patients with poor CYP450 2D6 activity demonstrate higher blood concentrations of flecainide and propafenone and have more side effects for a given dose than those with normal enzyme activity.1 2 Awareness of a patient's genotype can protect that patient from certain drugs or their prescription in dangerous doses. Pharmacogenetics extends this approach of tailoring drug development and treatment beyond factors that regulate drug metabolism to other genetically determined variables that may influence the response of a patient to a given drug.

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