Mondorf U F, Russ A, Wiesemann A, Herrero M, Oremek G, Lenz T
Division of Nephrology, Medizinische Klinik IV, Johann Wolfgang Goethe Universität, Frankfurt, Germany.
Am J Hypertens. 1998 Feb;11(2):174-83. doi: 10.1016/s0895-7061(97)00402-0.
The renin-angiotensin system (RAS) is involved in the pathogenesis of essential hypertension. In the present study we examined the genotype frequencies of the insertion/deletion polymorphisms of the ACE gene and the M235T polymorphism of the Angiotensinogen (Agt) gene in patients with essential hypertension in comparison with normotensive subjects. In hypertensive patients functional effects of blood pressure response to ACE inhibition were investigated. A total of 121 patients with essential hypertension (group 1) and 125 normotensive control subjects (group 2) were included in this study. All patients were genotyped by polymerase chain reactions (PCR) for the insertion/deletion (I/D) polymorphism of the ACE gene and the M235T polymorphism of the Agt gene. To analyze possible functional impacts on blood pressure regulation 50 mg of captopril was administered to hypertensive patients. No significant association of essential hypertension with polymorphisms of the Agt and ACE gene was found. The ACE serum levels in patients with the DD-genotype of the ACE I/D polymorphism were higher than in patients with the II-genotype (P < .01). In patients with the ID-genotype the ACE serum levels were in-between. A captopril test was performed in hypertensive patients. The patients were further divided into subgroups according to the diastolic and systolic blood pressure response. Group 1a consisted of patients with a diastolic blood pressure drop of > 5 mm Hg and group 1b with < or =5 mm Hg. Group 1c consisted of patients with a systolic blood pressure drop of > 10 mm Hg and group 1d with < or =10 mm Hg. Twice as many patients with the DD genotype of the ACE gene were found in group 1a compared to group 1b (chi(2) = 5.673; P = .017). No association of systolic blood pressure change to the investigated polymorphisms was found. Our results do not support the hypothesis that the investigated polymorphisms contribute to essential hypertension. Furthermore, no major impact of these polymorphisms on blood pressure response to captopril were detected. We conclude that the investigated genotypes have no influence on blood pressure level and homeostasis.
肾素-血管紧张素系统（RAS）参与原发性高血压的发病机制。在本研究中，我们检测了原发性高血压患者与血压正常受试者相比，血管紧张素转换酶（ACE）基因插入/缺失多态性和血管紧张素原（Agt）基因M235T多态性的基因型频率。在高血压患者中，研究了血压对ACE抑制反应的功能效应。本研究共纳入121例原发性高血压患者（第1组）和125例血压正常的对照受试者（第2组）。所有患者均通过聚合酶链反应（PCR）对ACE基因的插入/缺失（I/D）多态性和Agt基因的M235T多态性进行基因分型。为了分析对血压调节可能的功能影响，给高血压患者服用50 mg卡托普利。未发现原发性高血压与Agt和ACE基因多态性之间存在显著关联。ACE I/D多态性DD基因型患者的ACE血清水平高于II基因型患者（P <.01）。ID基因型患者的ACE血清水平介于两者之间。对高血压患者进行了卡托普利试验。根据舒张压和收缩压反应将患者进一步分为亚组。第1a组由舒张压下降>5 mmHg的患者组成，第1b组由舒张压下降≤5 mmHg的患者组成。第1c组由收缩压下降>10 mmHg的患者组成，第1d组由收缩压下降≤10 mmHg的患者组成。与第1b组相比，第1a组中ACE基因DD基因型的患者数量是其两倍（χ2 = 5.673；P = 0.017）。未发现收缩压变化与所研究的多态性之间存在关联。我们的结果不支持所研究的多态性导致原发性高血压的假说。此外，未检测到这些多态性对卡托普利血压反应的主要影响。我们得出结论，所研究的基因型对血压水平和内环境稳态没有影响。
