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

被引:469
作者
Inoue, I
Nakajima, T
Williams, CS
Quackenbush, J
Puryear, R
Powers, M
Cheng, T
Ludwig, EH
Sharma, AM
Hata, A
Jeunemaitre, X
Lalouel, JM
机构
[1] UNIV UTAH,HLTH SCI CTR,HOWARD HUGHES MED INST,ECCLES INST HUMAN GENET,SALT LAKE CITY,UT 84112
[2] UNIV UTAH,HLTH SCI CTR,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112
[3] FREE UNIV BERLIN,DEPT GEN INTERNAL MED & NEPHROL,D-12200 BERLIN,GERMANY
[4] HOKKAIDO UNIV,SCH MED,DEPT PUBL HLTH,SAPPORO,HOKKAIDO 070,JAPAN
[5] HOP BROUSSAIS,INSERM U36,F-75005 PARIS,FRANCE
[6] HOP BROUSSAIS,MOL BIOL LAB,F-75005 PARIS,FRANCE
关键词
essential hypertension; angiotensinogen; molecular variant; promoter; transcription;
D O I
10.1172/JCI119343
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 (1). 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.
引用
收藏
页码:1786 / 1797
页数:12
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