Genetic polymorphisms related to the renin-angiotensin-aldosterone system and response to antihypertensive drugs

Only 23 - 41% of hypertensive patients receiving antihypertensive drugs achieve adequate blood pressure control. Multiple physiological systems regulate blood pressure and variation in genes involved in these systems may account for enhanced or diminished blood pressure lowering response to antihypertensive therapy.

We explored explanations for variation in blood pressure response to antihypertensive drugs by linking genetic polymorphisms in renin-angiotensin-aldosterone system (RAAS) genes to antihypertensive drug response on intermediate parameters (e.g., potassium excretion, aldosterone levels). A MEDLINE search (1966 - 2008) was performed to identify publications reporting effects of genetic polymorphisms in the RAAS on antihypertensive drug response with regard to intermediate parameters.

With regard to the ACE insertion/deletion and the angiotensinogen -217G/A polymorphism variation in blood pressure response could be explained by effects on intermediate parameters. However, most studies that were identified with our search varied in study design, population and outcome, which complicate adequate comparisons.

Little evidence is available that explains these pharmacogenetic interactions. In the future, a better understanding of these mechanisms should provide a more solid evidence base for the individualized hypertension treatment based on genetic variation.