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

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/EBPβ or C/EBPδ 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.