Essential Hypertension and 5′ Upstream Core Promoter Region of Human Angiotensinogen Gene

Abstract

The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.

Association between renin–angiotensin system gene polymorphism and essential hypertension: a community-based study

“…9,10,13,14 Several functional studies have indicated that AGT A-6G, A-20C and G-217A polymorphisms in the promoter region play important roles in regulating the AGT gene transcription and expression. [17][18][19] In a recent study, Dickson et al 10 further testified the hypothesis that the polymorphisms in the AGT promoter may affect cell function, specifically regulation in the level of AGT transcription in AGT-producing tissues. We can assume that AGT gene transcription may be induced by the activity of several AGT gene variants, leading to the increased level of plasma AGT.…”

Polymorphisms of the angiotensinogen gene and the outcome of microalbuminuria in essential hypertension: a 3-year follow-up study

“…7,8 The molecular variants of the angiotensinogen (AGT) gene, a key component of the renninangiotensin system (RAS), are considered genetic risk factors for primary hypertension. 9 Polymorphisms of the coding and the promoter regions, M235T and A-6G, respectively, have been linked to the AGT plasma levels and to the risk of hypertension in several studies, [10][11][12][13][14] but not in others. 15,16 Crosssectional association studies, meanwhile, have reported a lack of impact of the polymorphisms of the AGT gene on microalbuminuria.…”

Epidemiological Study of AGT Gene Polymorphism among Chinese Subjects with Primary Hypertension

“…Aside from its roles in the renin angiotensin system in regulating salt metabolism, vascular permeability and sympathetic nervous system activity, AGT also plays an important role in the pathogenesis of hypertension [5,6]. Studies have focused on searching for the relationship between AGT polymorphism and susceptibility to hypertension [7,8]. Several studies have focused on different single nucleotide polymorphisms in the AGT promoter region, including -20 A→C, -18 C→T and -6 G→A substitutions.…”

“…In 1996, Yanai et al [7] discovered a nuclear factor (AGCF1) that binds to AGCE1 in the AGT transcription initiation site between positions -25 and ¬-1. Ishigami et al [8] reported that A-20C polymorphism is closely associated with EH and plasma AGT levels. Using human liver tumor cells, Zhao et al [9] observed that A→C substitution at position -20 in the AGT promoter led to an increase in AGT transcription.…”