GENETIC POLYMORPHISMS OF THE RENIN-ANGIOTENSIN SYSTEM

Gene coding for the main components of the reninangiotensin system hav e been characterized and localized: angiotensinogen (AGT, chromosome 1 q42), renin (REN, chromosome 1), angiotensin I-converting enzyme (ACE, chromosome 17), angiotensin II receptors (ATIR chromosome 3 and AT2R, chromosome X). A positive linkage and association have been found bet ween AGT and essential hypertension. M235T is also associated with pla sma AGT concentration. In vitro studies suggest that a polymorphism (G -6A) which is in complete linkage disequilibrium with M235T and which is located in the promoter close to the start of transcription might e xplain this association with high blood pressure. The ACE I/D polymorp hism explains about 30 to 40 per cent of the variance of plasma ACE le vels. Although the ACE gene itself does not seem to play a role in blo od pressure level, the corresponding chromosomal region has been linke d to blood pressure in both spontaneously hypertensive rats and humans . In tissues, an increased ACE activity may explain the association be tween the ACE I/D polymorphism and coronary heart disease, left ventri cular hypertrophy, neointimal proliferation in vessels and progression of diabetic and IgA nephropathy.