Angiotensinogen gene polymorphism at -217 affects basal promoter activity and is associated with hypertension in African-Americans.
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 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/EBPbeta 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.
Jain
Sudhir
S
Department of Pathology, New York Medical College, Valhalla, New York 10595, USA.
Tang
Xiangna
X
Narayanan
Chittampalli S
CS
Agarwal
Yogesh
Y
Peterson
Stephen M
SM
Brown
Clinton D
CD
Ott
Jurg
J
Kumar
Ashok
A
D000328:Adult; D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D044383:Black People; D002460:Cell Line; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014162:Transfection; D014481:United States; D001741:Black or African American
D009841:Oligonucleotides; D000808:Angiotensinogen