JCI - A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro.

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Inoue, I. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Nakajima, T. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Williams, C. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Quackenbush, J. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Puryear, R. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Powers, M. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Cheng, T. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Ludwig, E. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Sharma, A. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Hata, A. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Jeunemaitre, X. in: JCI | PubMed | Google Scholar

Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City 84112, USA.

Find articles by Lalouel, J. in: JCI | PubMed | Google Scholar

Abstract

In earlier studies, we provided statistical evidence that individual differences in the angiotensinogen gene, the precursor of the vasoactive hormone angiotensin II, constitute inherited predispositions to essential hypertension in humans. We have now identified a common variant in the proximal promoter, the presence of an adenine, instead of a guanine, 6 bp upstream from the initiation site of transcription, in significant association with the disorder. Tests of promoter activity and DNA binding studies with nuclear proteins suggest that this nucleotide substitution affects the basal transcription rate of the gene. These observations provide some biological insight about the possible mechanism of a genetic predisposition to essential hypertension; they may also have important evolutionary implications.