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/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.
Jain
Sudhir
S
Department of Pathology, New York Medical College, Basic Science Building, Valhalla, NY 10595, USA.
Li
Yanna
Y
Patil
Sai
S
Kumar
Ashok
A
D000808:Angiotensinogen / Q000235:genetics*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D015850:Interleukin-6 / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D017931:DNA Primers; D005938:Glucocorticoids; D015850:Interleukin-6; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins; D014157:Transcription Factors; D000808:Angiotensinogen; D051743:CCAAT-Enhancer-Binding Protein-delta; D003907:Dexamethasone