A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro
A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro
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DOI：
10.1172/jci119343
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发表时间：
1997-04-01
影响因子：
15.9
通讯作者：
Lalouel, JM
中科院分区：
文献类型：
--
作者：
Inoue, I;Nakajima, T;Lalouel, JM
在早期的研究中，我们提供了统计学证据，表明血管紧张素原基因（血管活性激素血管紧张素II的前体）的个体差异构成了人类原发性高血压的遗传易感性（1）。我们现在已经确定了一个常见的变体在近端启动子，腺嘌呤的存在下，而不是一个鸟嘌呤，上游6 bp的转录起始位点，在显着关联的障碍，启动子活性和DNA结合与核蛋白的研究表明，这种核苷酸取代影响的基础转录率的基因。这些观察结果提供了一些生物学的见解，遗传易感性原发性高血压的可能机制，他们也可能有重要的进化意义。
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.