Significance of genetic polymorphisms of the renin-angiotensin-aldosterone system in cardiovascular and renal disease.
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.
Rudnicki
Michael
M
Department of Internal Medicine IV, (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
Mayer
Gert
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D002353:Carrier State; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000235:genetics; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000235:genetics; D015994:Incidence; D007674:Kidney Diseases / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics*; D018570:Risk Assessment
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A