The genes of the renin-angiotensin-aldosterone system are involved in the pathogenesis of human hypertension. Abnormalities of two genes related to this system, and involved in aldosterone biosynthesis and action, are directly responsible for two autosomal dominant forms of hypertension: glucocorticoid suppressible hypertension and Liddle's syndrome. In familial essential hypertension, neither the renin nor the angiotensin I converting enzyme (ACE) genes contribute to a large extent to genetic hypertension. Although the ACE gene does not seem to be involved in the genetics of hypertension, an ACE gene polymorphism is associated with increased plasma ACE levels and appears to be a strong marker of coronary and cardiac diseases and diabetic complications. Angiotensinogen gene polymorphism appears to be linked to hypertension, and molecular variants of the protein are associated with high blood pressure in various populations and ethnic groups. An angiotensin II receptor variant (AT1) is also associated with essential hypertension. This gene variant, together with ACE gene polymorphism, increases the relative risk of myocardial infarction. Altogether, these recent results suggest that variants of the renin-angiotensin system genes are directly or indirectly responsible for a genetic predisposition to cardiovascular diseases. They may overstimulate the plasma and tissular renin system, which would in turn favor the development of high blood pressure.
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