Angiotensinogen Gene Polymorphism at −217 Affects Basal Promoter Activity and Is Associated with Hypertension in African-Americans
Journal of Biological Chemistry
Hypertension is a serious health problem in Western society, in particular for the African-American population. Although previous studies have suggested that the angiotensinogen (AGT) gene locus is involved in human essential hypertension, the molecular mechanisms involved in hypertension in African-Americans remain unknown. We show that an A/G polymorphism at ؊217 in the promoter of the AGT gene plays a significant role in hypertension in African-Americans. The frequency of the ؊217A allele
... the ؊217A allele was increased significantly in African-American hypertensive subjects compared with normotensive controls. We also show that the nucleotide sequence of this region of the AGT gene promoter bound strongly to CAAT/enhancer-binding protein (C/EBP) family transcription factors when nucleoside A was present at ؊217. In addition, we show that reporter constructs containing the human AGT gene promoter with nucleoside A at ؊217 had increased basal transcriptional activity upon transient transfection in HepG2 cells compared with reporter constructs with nucleoside G at ؊217. Finally, we show that interleukin-6 treatment in the presence or absence of overexpressed C/EBP␤ increased the promoter activities of reporter constructs containing nucleoside A at ؊217 compared with reporter constructs containing nucleoside G at ؊217. Because the AGT gene is expressed primarily in liver and adipose tissue, and C/EBP family transcription factors play an important role in gene expression in these tissues, we propose that increased transcriptional activity of the ؊217A allele of the human AGT gene is associated with hypertension in African-Americans.