Antihypertensive Drug-Gene Interactiosn and Cardiovascular Outcomes

Hypertension is a major public health hazard, because of its high prevalence and strong positive association with cardiovascular diseases. Suboptimal blood pressure control is the number one attributable risk for death in the Western world, despite the possibilities to treat hypertension. Higher pre-treatment blood pressure levels are associated with a greater antihypertensive drug response, but this relation is not specific to a particular antihypertensive drug or drug class nor can it be predicted from patients characteristics. Therefore, the selection of the most appropriate pharmacological treatment for an individual patient is a matter of trial and errors. Pharmacogenetics aims to understand how genetic variations contribute to the variation in response to medication. In this thesis, we investigated whether five of these drug-gene interactions modified the effect of antihypertensive drugs on blood pressure, atherosclerosis, and the risk of myoc! ardial infarction (MI) and stroke in daily practise. The five candidate gene polymorphisms were: the angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T, angiotensin II receptor type 1 (AGTR1) 1166A/C or 573C/T, a-adducin (ADD1) G460W, and β3-subunit of the G-protein (GNB3) 825C/T polymorphism. The results of this thesis suggests the presences of two drug-gene interactions i.e. the interaction between the use of ACE-inhibitors and AGT M235T polymorphism on the risk of MI and the interaction between the use of diuretics and the GNB3 825C/T polymorphism on systolic blood pressure.

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