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

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.

• Authors: Sudhir Jain, Yanna Li, Sai Patil, Ashok Kumar
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 83 Issue 2 Pg. 121-31 (Feb 2005) ISSN: 0946-2716 [Print] Germany
• PMID: 15630592 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CCAAT-Enhancer-Binding Protein-beta
• CCAAT-Enhancer-Binding Proteins
• CEBPD protein, human
• DNA Primers
• Glucocorticoids
• Interleukin-6
• Receptors, Glucocorticoid
• Recombinant Proteins
• Transcription Factors
• Angiotensinogen
• CCAAT-Enhancer-Binding Protein-delta
• Dexamethasone

Topics

• Angiotensinogen (genetics)
• CCAAT-Enhancer-Binding Protein-beta (metabolism)
• CCAAT-Enhancer-Binding Protein-delta
• CCAAT-Enhancer-Binding Proteins (metabolism)
• Carcinoma, Hepatocellular (genetics, metabolism)
• Cells, Cultured
• DNA Primers (chemistry)
• Dexamethasone (pharmacology)
• Gene Expression Regulation
• Glucocorticoids (pharmacology)
• Humans
• Hypertension (genetics)
• Interleukin-6 (pharmacology)
• Kidney (metabolism)
• Liver Neoplasms (genetics, metabolism)
• Mutation (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Promoter Regions, Genetic
• Receptors, Glucocorticoid (metabolism)
• Recombinant Proteins (metabolism)
• Regulatory Sequences, Nucleic Acid
• Transcription Factors (metabolism)
• Transcription, Genetic
• Transfection