Implications of the angiotensinogen gene in blood pressure regulation

Essential hypertension is a complex disease influenced by different genetic and environmental factors. The renin-angiotensin system (RAS) is implicate d in blood pressure regulation. Angiotensinogen (AGT) is the precursor of the biologically active angiotens in II (Ang II). Initial studies on hypertensive siblings and case-control s tudies indicated the important role of the angiotensinogen gene (AGT) for t he predisposition to essential hypertension, preeclampsia and obesity-relat ed hypertension. Recently, different AGT poly morphisms had been identified and analyzed in case-control studies. The aim of present studies is the an alysis of potentially functional AGT variants (C-532T, G-6A), which might b e responsible for the regulation of gene expression and therefore AGT gener ation. The A-6 allele is in complete linkage disequilibrium with the T235 a llele and is associated with higher AGT expression in vitro. Segregation li nkage analysis demonstrated that the C-532T polymorphism influences plasma AGT variability more significantly than the G-6A variant. Since the C-532T polymorphism is located within a AP-2 consensus element, functional promote r analyses are required. The understanding of the molecular basis of RAS in essential hypertension m ay provide us with new and more specific pharmacological agents and perhaps the ability to individualize antihypertensive treatment.