Ishigami T, Umemura S, Tamura K, Hibi K, Nyui N, Kihara M, Yabana M, Watanabe Y, Sumida Y, Nagahara T, Ochiai H, Ishii M
Second Department of Internal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
Hypertension. 1997 Dec;30(6):1325-30. doi: 10.1161/01.hyp.30.6.1325.
The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.
血管紧张素原（AGT）基因M235T变异与原发性高血压及血浆AGT浓度升高相关，但其潜在机制尚不清楚。最近的研究表明，位于人类AGT基因5'上游核心启动子区域（位置-25至-1）的AGCE 1（人类AGT基因核心启动子元件1）通过与转录因子AGCF 1（人类AGT基因核心启动子元件结合因子1）结合，在AGT mRNA的表达中起重要作用，并且在-20位由腺嘌呤突变为胞嘧啶（A-20C）会增加该转录本的表达水平。因此，我们对有这种突变的受试者进行了检查，以研究其与血浆AGT浓度升高及原发性高血压的关系。对188名未接受抗高血压药物治疗的受试者进行了A-20C与血浆AGT浓度之间相关性的检查，并对234名受试者进行了A-20C与原发性高血压之间关系的研究。通过使用EcoOR 109I的聚合酶链反应-限制性片段长度多态性分析来确定A-20C。多元回归分析显示A-20C与血浆AGT浓度（P = 0.047）和原发性高血压（P = 0.049）之间存在微弱但显著的相关性。结果表明，A-20C可能是血浆AGT浓度升高的基础，并参与原发性高血压的发生发展。
