Yoshida H, Kuriyama S, Atsumi Y, Tomonari H, Mitarai T, Hamaguchi A, Kubo H, Kawaguchi Y, Kon V, Matsuoka K, Ichikawa I, Sakai O
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Kidney Int. 1996 Aug;50(2):657-64. doi: 10.1038/ki.1996.362.
A total of 168 patients with non-insulin dependent diabetes (NIDDM) followed over 10 years were recruited in this study. The patients were divided into two groups: Group 1 patients had a stable renal function (N = 96) and Group 2 had a declining renal function (N = 72). Group 1 included those whose serum creatinine was normal five years ago but had increased to > or = 2 mg/dl or those who has reached end-stage renal failure (requiring dialysis) by the time of study. All patients were genotyped for the insertion/deletion (I/D) polymorphism of the ACE gene, the M235T polymorphism of the angiotensinogen (Atg) gene and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1) gene. The genotype frequency distributions of M235T Atg and the A116C AT1 gene polymorphisms were not different between Group 1 versus Group 2. While the frequency of the ACE DD genotype in Group 1 (7.3%) was comparable to that of the general population, the DD frequency was significantly higher in Group 2 (26.4%) than in Group 1 (odds ratio, 4.56; 95% confidence interval, 1.80 approximately 11.56, P < 0.001). Among all 168 patients studied, the renal survival rate was significantly lower among DD than ID (P < 0.005) or II patients (P < 0.001). In patients with a declining renal function (Group 2), those with the DD genotype had a significantly shorter time interval from onset of diabetes to the initiation of dialysis (13.4 +/- 1.4 years) than those with ID (20.7 +/- 1.2 years, P < 0.01) or II genotypes (17.5 +/- 1.1 year, P < 0.01). Analysis of the clinical course of the three ACE genotypes revealed that the majority (95%) of patients with the DD genotype who had albuminuria progressed to end-stage renal disease within 10 years of diagnosis of diabetes. Our analysis also revealed that initiation and continuation of dialysis are associated with a progressive decrease in the frequency of the DD genotype. These results indicate that, in NIDDM, the ACE DD genotype has a high prognostic value for progressive deterioration of renal function. Moreover, the DD genotype appears to increase the mortality once dialysis is initiated.
本研究招募了168例非胰岛素依赖型糖尿病（NIDDM）患者，随访时间超过10年。患者被分为两组：第1组患者肾功能稳定（N = 96），第2组患者肾功能呈下降趋势（N = 72）。第1组包括那些五年前血清肌酐正常但已升至≥2mg/dl的患者，或在研究时已达到终末期肾衰竭（需要透析）的患者。所有患者均进行了ACE基因插入/缺失（I/D）多态性、血管紧张素原（Atg）基因M235T多态性和血管紧张素II 1型受体（AT1）基因A1166C多态性的基因分型。第1组和第2组之间M235T Atg和A116C AT1基因多态性的基因型频率分布没有差异。第1组中ACE DD基因型的频率（7.3%）与普通人群相当，而第2组中DD频率（26.4%）显著高于第1组（优势比，4.56；95%置信区间，1.80至11.56，P < 0.001）。在所有168例研究患者中，DD基因型患者的肾脏存活率显著低于ID（P < 0.005）或II基因型患者（P < 0.001）。在肾功能下降的患者（第2组）中，DD基因型患者从糖尿病发病到开始透析的时间间隔（13.4±1.4年）显著短于ID基因型患者（20.7±1.2年，P < 0.01）或II基因型患者（17.5±1.1年，P < 0.01）。对三种ACE基因型临床病程的分析显示，大多数（95%）有蛋白尿的DD基因型患者在糖尿病诊断后的10年内进展为终末期肾病。我们的分析还显示，透析的开始和持续与DD基因型频率的逐渐降低有关。这些结果表明，在NIDDM中，ACE DD基因型对肾功能的进行性恶化具有较高的预后价值。此外，DD基因型似乎会增加透析开始后的死亡率。
