A Haplotype of the Angiotensinogen Gene Is Associated With Hypertension in African Americans

Abstract

1. Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke and renal failure. The incidence of hypertension is 25-30% in the adult Caucasian population and complications due to hypertension are even greater in African Americans. 2. The renin-angiotensin system plays an important role in the regulation of blood pressure and previous studies have suggested that angiotensinogen (AGT) gene locus is linked with human essential hypertension. Earlier studies suggested that a single nucleotide polymorphism (SNP) that converts methionine to threonine at amino acid 235 is associated with hypertension in the Caucasian population. However, this SNP is not associated with hypertension in African American and Chinese populations. 3. We have found an A/G polymorphism at -217 of the human AGT gene promoter and have shown that the frequency of allele A at -217 is significantly increased in the genomic DNA of African American hypertensive patients. 4. We have also shown that: (i) reporter constructs containing the AGT gene promoter with nucleoside A at -217 have increased promoter activity on transient transfection; and (ii) the CCAAT box enhancer binding protein (C/EBP) family of transcription factors and glucocorticoid receptor (GR) bind preferentially to this region of the promoter when nucleoside A is present at -217. In addition, variant -217A is always present with variants -532T, -793A and -1074T in the human AGT gene promoter. 5. These data suggest that the AGT haplotype containing -217A, -532T, -793A and -1074T may be involved in increased transcription of this gene and may play a role in human hypertension.

The effect of genetic variation in angiotensinogen on serum levels and blood pressure: a comparison of Nigerians and US blacks

“…13,[29][30][31] Two recent studies involving African-American samples reported associations between the H1 haplotype (the variants that defined the associated haplotype in both studies are the ones that define our H1) and HT. 32,33 Our study also found an association between H1 and HT in the sample of African Americans. The fact that two other recent studies observed, this association is very encouraging given the long history of inconsistent results between studies for the AGT gene.…”

Estimation of risk and interaction of single nucleotide polymorphisms at angiotensinogen locus causing susceptibility to essential hypertension: a case control study

“…Further, a study data involving African Americans suggested that the AGT haplotypes containing -217A, -532T, -793A and -1074T may be involved in increased transcription of the AGT gene and may play a role in human hypertension. 77 In conclusion, this study revealed a high risk of EHT for males with AA genotypes of -217G>A polymorphism. This indicates that the earlier report of strong binding of C/EBP family transcription factor with nucleoside A resulting in increased expression of -217A in hypertensives may be gender specific.…”

Role of Angiotensin Peptides Precursor in Ethanol Mediated Hepato toxicity: Perspective on Angiotensinogen

“…In addition to the aforementioned SNP and its significance in the transcriptional regulation of human AGT, a number of other SNPs [-1074 T/G, -793 A/G and -776 C/T] have also been reported. SNP -1074T binds to HNF3β while -1074G lacks the binding ability [97].…”

“…(2). Some of the studies which have been carried out from Kumar lab and others have defined the role of transcription factors which are involved in the regulation of organ specific AGT expression [97]. CAAT enhancer binding protein [C/EBP] family of transcription factors especially C/EBPbinds to the sequences at -99 to -91 of human AGT gene promoter [98] .…”