Pharmacogenomics and Cardiovascular Drugs
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Cardiovascular diseases are a large group of multifactorial pathologies. Thus, it is not surprising that more than 13 classes and many subclasses of drugs have been developed in this field. However, the responses to these drugs differ significantly between patients.
Five groups of genes are involved in these different responses:
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The genes regulating the pharmacokinetics phase of the drug. Cytochromes P450, 2D6, and C9–C19 are the most frequently involved. However, transporters like ABC families also have to be taken into account.
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| 2. |
The genes related to the pharmacodynamics phase. The enzymes inhibited by the drugs (angiotensine converting enzyme, HMG CoA reductase) the receptors involved in their actions (β-adrenergic receptors, angiotensine I and II receptors) and the lipoproteins modified in their expression levels in plasma (apolipoprotein E, apolipo-protein B, apolipoprotein CIII, CETP) are also important pharmacogenomic targets.
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Pathologies and metabolic pathways related to gene polymorphisms from the patients under treatment introduce a third range of pharmacological variability, i.e., inflammation pathway genes.
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Health and physiological mechanisms (i.e., age, gender, ethnicity, weight) could modify the gene polymorphisms' effects.
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Finally, genes environmentally sensitive to diet, tobacco, pollutants, etc., are important and interfere in the pharmacogenomic response of many drugs.
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The development of new cardiovascular drugs and the survey of some existing ones should take into account some of these polymorphisms in order to adapt the drug dosage to each individual and to avoid drug side effects.
