van der Kleij Frank G H, de Jong Paul E, Henning Rob H, de Zeeuw Dick, Navis Gerjan
*Groningen University Institute for Drug Exploration, Department of Internal Medicine, Division of Nephrology, and Department of Clinical Pharmacology, University Hospital Groningen and State University Groningen, Groningen, The Netherlands.
J Am Soc Nephrol. 2002 Apr;13(4):1025-1033. doi: 10.1681/ASN.V1341025.
Angiotensin-converting enzyme (ACE) activity is increased in the DD genotype, but the functional significance for renal function is unknown. Blunted responses of BP and proteinuria to ACE inhibition among DD renal patients during periods of high sodium intake were reported. It was therefore hypothesized that sodium status affects the phenotype in the ACE I/D polymorphism. The effects of angiotensin I (AngI) and AngII among 27 healthy subjects, with both low (50 mmol sodium/d) and liberal (200 mmol sodium/d) sodium intakes, were studied. Baseline mean arterial pressure (MAP) values, renal hemodynamic parameters, and renin-angiotensin system parameters were similar for all genotypes with either sodium intake level. With liberal sodium intake, the increases in MAP, renal vascular resistance, and aldosterone levels during AngI infusion (8 ng/kg per min) were significantly higher for the DD genotype, compared with the ID and II genotypes (all parameters presented as percent changes +/- 95% confidence intervals), with mean MAP increases of 22 +/- 2% (DD genotype), 13 +/- 5% (ID genotype), and 12 +/- 6% (II genotype) (P < 0.05), mean increases in renal vascular resistance of 100.1 +/- 19.7% (DD genotype), 73.0 +/- 16.3% (ID genotype), and 63.2 +/- 16.9% (II genotype) (P < 0.05), and increases in aldosterone levels of 650 +/- 189% (DD genotype), 343 +/- 71% (ID genotype), and 254 +/- 99% (II genotype) (P < 0.05). Also, the decrease in GFR was more pronounced for the DD genotype, with mean decreases of 17.9 +/- 4.7% (DD genotype), 8.8 +/- 3.4% (ID genotype), and 6.4 +/- 5.9% (II genotype) (P < 0.05). The effective renal plasma flow, plasma AngII concentration, and plasma renin activity values were similar for the genotypes. In contrast, with low sodium intake, the responses to AngI were similar for all genotypes. The responses to AngII were also similar for all genotypes, with either sodium intake level. In conclusion, the responses of MAP, renal hemodynamic parameters, and aldosterone concentrations to AngI are enhanced for the DD genotype with liberal but not low sodium intake. These results support the presence of gene-environment interactions between ACE genotypes and dietary sodium intake.
血管紧张素转换酶（ACE）活性在DD基因型中升高，但对肾功能的功能意义尚不清楚。有报道称，DD基因型肾病患者在高钠摄入期间对ACE抑制的血压和蛋白尿反应减弱。因此，有人提出假设，钠状态会影响ACE I/D多态性的表型。研究了27名健康受试者在低钠（50 mmol钠/天）和高钠（200 mmol钠/天）摄入情况下，血管紧张素I（AngI）和血管紧张素II（AngII）的作用。在两种钠摄入水平下，所有基因型的基线平均动脉压（MAP）值、肾血流动力学参数和肾素-血管紧张素系统参数相似。高钠摄入时，与ID和II基因型相比，DD基因型在输注AngI（8 ng/kg每分钟）期间MAP、肾血管阻力和醛固酮水平的升高显著更高（所有参数以百分比变化±95%置信区间表示），平均MAP升高分别为22±2%（DD基因型）、13±5%（ID基因型）和12±6%（II基因型）（P<0.05），肾血管阻力平均升高分别为100.1±19.7%（DD基因型）、73.0±16.3%（ID基因型）和63.2±16.9%（II基因型）（P<0.05），醛固酮水平升高分别为650±189%（DD基因型）、343±71%（ID基因型）和254±99%（II基因型）（P<0.05）。此外，DD基因型的肾小球滤过率（GFR）下降更明显，平均下降分别为17.9±4.7%（DD基因型）、8.8±3.4%（ID基因型）和6.4±5.9%（II基因型）（P<0.05）。各基因型的有效肾血浆流量、血浆AngII浓度和血浆肾素活性值相似。相反，低钠摄入时，所有基因型对AngI的反应相似。在两种钠摄入水平下，所有基因型对AngII的反应也相似。总之，高钠而非低钠摄入时，DD基因型对AngI的MAP、肾血流动力学参数和醛固酮浓度反应增强。这些结果支持ACE基因型与饮食钠摄入之间存在基因-环境相互作用。
