Pharmacogenetics of Antihypertensive Therapies: Can this be Applied in the Clinic?

Blood pressure responses to antihypertensive drugs vary widely between individuals. Certain phenotypic factors may predict some drug responses such as plasma renin activity (PRA) as an indicator of activation of the reninangiotensin- aldosterone system. Higher PRA levels may predict better average responses to angiotensin converting enzyme inhibitors, angiotensin receptor blockers or β-blockers. Conversely, high salt intake or salt sensitivity may predict a better response to diuretics and calcium channel blockers. Genetic factors influencing the pharmacokinetics of specific drugs through enzymes or transporters or the pharmacodynamics of drug classes through receptors or pathways involved in the mechanism of drug action can also affect blood pressure responses, but the effects of most candidate genes are limited. Furthermore, the need to choose the most effective first-line antihypertensive agent becomes less critical with the awareness that most hypertensive patients will require a combination of drugs and drug combinations with complementary modes of action should help to overcome the major mechanisms driving hypertension. However, there may be situations where genotypes in pathways that may not be directly related to the blood pressure lowering effect may predict cardiovascular benefits with certain drugs. Currently, there are probably no genetic factors which dictate the use of a particular antihypertensive drug, except in some of the rare monogenic causes of hypertension. With the rapid expansion of pharmacogenetic knowledge, this situation is likely to change and specific targeted treatments may be selected based on combined genetic and phenotypic factors for individualizing long-term therapy for hypertension.