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

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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/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.

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Abbreviations

AGT :

Angiotensinogen

C/EBP :

CCAAT/enhancer-binding protein

CBP :

CREB-binding protein

CREB :

cAMP-response element binding protein

GR :

Glucocorticoid receptor

HEK :

Human embryonic kidney

hr :

Human recombinant

11-β HSD :

11-β Hydroxysteroid dehydrogenase

STAT :

Signal transducer and activator of transcription

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Acknowledgements

This work was supported by research grants HL 49884 and 59547 from the National Heart, Lung, and Blood Institute and from Philip-Morris Incorporated (to A.K.). We are thankful to Drs. K. Yamamoto, P. F. Johnson, and Steven McKnight for expression vectors.

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  1. Department of Pathology, New York Medical College, Basic Science Building, Valhalla, NY, 10595, USA

    Sudhir Jain, Yanna Li, Sai Patil & Ashok Kumar

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  1. Sudhir Jain
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  2. Yanna Li
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  3. Sai Patil
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  4. Ashok Kumar
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Correspondence to Ashok Kumar.

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Jain, S., Li, Y., Patil, S. et al. A single-nucleotide polymorphism in human angiotensinogen gene is associated with essential hypertension and affects glucocorticoid induced promoter activity. J Mol Med 83, 121–131 (2005). https://doi.org/10.1007/s00109-004-0621-5

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  • DOI: https://doi.org/10.1007/s00109-004-0621-5

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