Genetic polymorphisms in the renin-angiotensin system: relevance for susceptibility to cardiovascular disease.

The renin-angiotensin system plays an important role in the pathogenesis of cardiovascular disease. Cloning of the human genes coding for the angiotensin-converting enzyme, angiotensinogen, and angiotensin II type 1 receptor has led to the discovery of several polymorphisms, which may be implicated in the pathogenesis of cardiovascular disease. The deletion/insertion (D/I) polymorphism of the angiotensin-converting enzyme gene is associated with hypertension in men, left ventricular hypertrophy in untreated hypertensive patients, various atherosclerotic cardiovascular complications, and microvascular disorders. The M235T polymorphism of the angiotensinogen gene may be associated with a higher risk of hypertension. The A1166C polymorphism of the angiotensin II type 1 receptor gene is probably correlated with hypertension and through an epistatic interaction with the D/I polymorphism of the angiotensin-converting enzyme gene possibly also with coronary heart disease. Several other gene polymorphisms, in particular those in the promoter area of the angiotensinogen gene, have been studied in relation to cardiovascular disease. Based on the insights gained from the reports summarized in this review article, population-based genetic studies of nuclear families are currently being conducted in Belgium and in the People's Republic of China with blood pressure and hypertension as the main outcome variables.