Tang W H Wilson, Vagelos Randall H, Yee Yin-Gail, Fowler Michael B
Kaufman Center for Heart Failure, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Am Heart J. 2004 Nov;148(5):889-94. doi: 10.1016/j.ahj.2004.05.020.
The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear.
ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup.
At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P < .05). However, predose and postdose ALDO and A-II levels did not differ between each genotype subgroup at baseline or by enalapril dose within each genotype subgroup. ALDO escape and A-II reactivation were not affected by ACE genotype or enalapril dosage.
Predose sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.
血管紧张素转换酶（ACE）基因多态性对ACE抑制剂治疗的神经激素剂量反应的影响尚不清楚。
在74例慢性心力衰竭患者中确定ACE插入（I）或缺失（D）基因型，这些患者被随机分配接受高剂量或低剂量依那普利治疗6个月。比较基因型亚组之间以及每个基因型亚组内接受高剂量或低剂量依那普利的患者之间依那普利治疗前和治疗后每月的神经激素水平（血清ACE活性（sACE）、血浆血管紧张素II（A-II）、血浆肾素活性（PRA）和血清醛固酮（ALDO））。
基线时，DD基因型患者的治疗前/治疗后sACE和治疗后PRA显著更高。在6个月随访时，所有三种基因型的治疗后sACE均呈剂量依赖性降低（P <.05）。然而，各基因型亚组在基线时或每个基因型亚组内依那普利剂量之间的治疗前和治疗后ALDO及A-II水平并无差异。ALDO逃逸和A-II再激活不受ACE基因型或依那普利剂量的影响。
与ID或II亚组相比，DD基因型患者的治疗前sACE始终更高。尽管sACE受到剂量依赖性抑制，但在每个亚组中，随着依那普利剂量增加，未观察到ALDO和A-II抑制或逃逸方面有统计学显著差异。
