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Pharmacogenomics. 2009 Mar;10(3):463-76. doi: 10.2217/14622416.10.3.463.

Significance of genetic polymorphisms of the renin-angiotensin-aldosterone system in cardiovascular and renal disease.

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Department of Internal Medicine IV, (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.


The angiotensin converting enzyme (ACE) is a component of the renin-angiotensin-aldosterone system (RAAS). The RAAS--involved primarily in blood pressure and sodium homeostasis--is activated in many renal and cardiovascular diseases, and therapy with ACE inhibitors and other blockers of the RAAS has proven to be clinically beneficial. Plasma and tissue levels of ACE are at least partially determined by a genetic polymorphism based on the presence (insertion [I]) or absence (deletion [D]) of a 287 base pair element in intron 16. In particular Asian subjects with the DD genotype (and increased ACE activity) have been reported to be at higher risk for cardiovascular disorders and nephropathy. Numerous studies evaluated the role of the ACE I/D polymorphism as well as other genetic variants of the RAAS in the context of RAAS inhibitor therapy. However, as race and environmental factors, such as salt intake also affect treatment response most studies were underpowered leading to conflicting results.

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