van Essen G G, Rensma P L, de Zeeuw D, Sluiter W J, Scheffer H, Apperloo A J, de Jong P E
Department of Medicine, State University Hospital, Groningen, Netherlands.
Lancet. 1996 Jan 13;347(8994):94-5. doi: 10.1016/s0140-6736(96)90213-5.
Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a trial of long-term therapy with an ACE inhibitor or a beta-blocker.
81 patients with non-diabetic renal disease had been entered into a randomised comparison of oral atenolol or enalapril to prevent progressive decline in renal function. The dose was titrated to a goal diastolic blood pressure of 10 mm Hg below baseline and/or below 95 mm Hg. The mean (SE) age was 50 (1) years, and the group included 49 men. Their renal function had been monitored over 3-4 years. We have looked at their ACE genotype, which we assessed with PCR.
27 patients had the II genotype, 37 were ID, and 17 were DD. 11 patients were lost to follow-up over 1-3 years. The decline of glomerular filtration rate over the years was significantly steeper in the DD group than in the ID and the II groups (p = 0.02; means -3.79, -1.37, and -1.12 mL/min per year, respectively). The DD patients treated with enalapril fared as equally a bad course as the DD patients treated with atenolol. Neither drug lowered the degree of proteinuria in the DD group.
Our data show that patients with the DD genotype are resistant to commonly advocated renoprotective therapy.
血管紧张素转换酶（ACE）基因多态性，尤其是DD基因型，与心血管疾病风险相关。肾小球硬化与动脉粥样硬化有相似之处，我们研究了接受ACE抑制剂或β受体阻滞剂长期治疗的肾病患者的ACE基因多态性。
81例非糖尿病肾病患者进入口服阿替洛尔或依那普利预防肾功能进行性下降的随机对照试验。剂量滴定至目标舒张压比基线低10 mmHg和/或低于95 mmHg。平均（SE）年龄为50（1）岁，该组包括49名男性。他们的肾功能已监测3 - 4年。我们研究了他们的ACE基因型，通过PCR进行评估。
27例患者为II基因型，37例为ID基因型，17例为DD基因型。11例患者在1 - 3年的随访中失访。多年来，DD组肾小球滤过率的下降明显比ID组和II组更陡峭（p = 0.02；平均每年分别为-3.79、-1.37和-1.12 mL/min）。接受依那普利治疗的DD患者与接受阿替洛尔治疗的DD患者病情同样糟糕。两种药物均未降低DD组的蛋白尿程度。
我们的数据表明，DD基因型患者对普遍提倡的肾脏保护治疗有抵抗性。
