A single-nucleotide polymorphism in human angiotensinogen gene is associated with essential hypertension and affects glucocorticoid induced promoter activity

CCAAT-Enhancer-Binding Protein-delta 0301 basic medicine 0303 health sciences Carcinoma, Hepatocellular Interleukin-6 CCAAT-Enhancer-Binding Protein-beta Liver Neoplasms Angiotensinogen Kidney Polymorphism, Single Nucleotide Dexamethasone Recombinant Proteins 3. Good health 03 medical and health sciences Receptors, Glucocorticoid Gene Expression Regulation Hypertension Mutation CCAAT-Enhancer-Binding Proteins Humans Promoter Regions, Genetic Glucocorticoids Cells, Cultured DNA Primers
DOI: 10.1007/s00109-004-0621-5 Publication Date: 2005-01-03T15:42:26Z
ABSTRACT
Hypertension is a serious health problem particularly for African-Americans. Previous studies have suggested that angiotensinogen (AGT) gene locus is involved in human essential hypertension. We have recently shown that an A/G polymorphism at -217 in the promoter of the AGT gene is associated with essential hypertension especially in African-Americans. We report here that A/G polymorphism at -217 affects the glucocorticoid-induced promoter activity of the human AGT gene. We show that recombinant glucocorticoid receptor (GR) binds strongly to the AGT gene promoter when nucleoside A is present at -217, and dexamethasone treatment increases the interleukin 6 induced promoter activity of reporter constructs containing nucleoside A at -217. Similarly cotransfection of GR and C/EBP beta or C/EBP delta increases the promoter activity of reporter construct containing nucleoside A at -217. Since AGT is an acute phase protein, we propose that increased expression of -217A allele of the AGT gene by glucocorticoids and C/EBP family of transcription factors may be involved in essential hypertension.
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