Park Hyeong Cheon, Choi So Rae, Kim Beom Seok, Lee Tae Hee, Kang Byung Seung, Choi Kyu Hyun, Lee Ho Yung, Han Dae Suk, Ha Sung-Kyu
Department of Internal Medicine, Yongdong Severance Hospital, Yonsei University College of Medicine, 146-92 Dogok-dong, Gangnam-gu, Seoul, Korea.
Yonsei Med J. 2005 Dec 31;46(6):779-87. doi: 10.3349/ymj.2005.46.6.779.
The angiotensin-converting enzyme (ACE) gene DD homozygote has been suggested to be a significant risk factor for the progression of diabetic nephropathy. We analyzed clinical parameters and ACE genotype distribution between type 2 diabetic patients at the extremes of renal risk, i.e. an end-stage renal failure (ESRF) group (n = 103, group 1) who were on dialysis therapy due to progression of diabetic nephropathy, and a no progression group (n = 88, group 2) who had maintained normal renal function and normoalbuminuria for more than 15 years. There were no significant differences in age, sex, body mass index, HbA1c level, or lipid profiles between the two groups (p > 0.05). Group 1 had a significantly higher prevalence of hypertension [group 1: 82.5% (85/103) vs. group 2: 50.0% (44/88), p < 0.05] and diabetic retinopathy [group 1: 103/103 (100%) vs. group 2: 28/88 (31.8%), p < 0.05] than group 2. Daily urinary albumin excretion was also higher in group 1 than in group 2 [group 1: 2873 +/- 2176 mg/day vs. 12 +/- 7 g/day, p < 0.05]. The frequencies of the DD, ID, and II genotypes of the ACE gene in group 1 and group 2 were 26.2%, 47.6%, and 26.2%, and 7.9%, 57.9%, and 34.2%, respectively. The ACE genotype frequencies between the two groups were significantly different according to a chi-square test with Bonferroni's correction (p = 0.004). The presence of the DD genotype increased the risk of ESRF 4.286-fold compared to the II genotype [odds ratio 4.286, 95% CI 1.60- 11.42, p = 0.005]. The frequency of the D-allele was higher in both male and female patients in group 1 compared to group 2, but reached statistical significance only in males [male, group 1: 50.8% vs. group 2: 35.0%, p = 0.018, female, group 1: 48.8% vs. group 2: 39.5%, p = 0.231]. This study, although limited by sample size, showed that type 2 diabetic ESRF patients more frequently expressed the DD genotype. These findings may substantiate the previously noted relationship between the ACE DD genotype and the progression of diabetic nephropathy in Korean type 2 diabetic patients.
血管紧张素转换酶（ACE）基因DD纯合子被认为是糖尿病肾病进展的一个重要危险因素。我们分析了处于肾脏风险极端状态的2型糖尿病患者的临床参数和ACE基因型分布，即终末期肾衰竭（ESRF）组（n = 103，第1组），这些患者因糖尿病肾病进展而接受透析治疗，以及无进展组（n = 88，第2组），他们维持正常肾功能和正常白蛋白尿超过15年。两组在年龄、性别、体重指数、糖化血红蛋白水平或血脂谱方面无显著差异（p > 0.05）。第1组的高血压患病率[第1组：82.5%（85/103） vs. 第2组：50.0%（44/88），p < 0.05]和糖尿病视网膜病变患病率[第1组：103/103（100%） vs. 第2组：28/88（31.8%），p < 0.05]均显著高于第2组。第1组的每日尿白蛋白排泄量也高于第2组[第1组：2873 ± 2176 mg/天 vs. 12 ± 7 g/天，p < 0.05]。第1组和第2组中ACE基因的DD、ID和II基因型频率分别为26.2%、47.6%和26.2%，以及7.9%、57.9%和34.2%。经Bonferroni校正的卡方检验显示，两组之间的ACE基因型频率有显著差异（p = 0.004）。与II基因型相比，DD基因型的存在使ESRF风险增加4.286倍[比值比4.286，95%置信区间1.60 - 11.42，p = 0.005]。与第2组相比，第1组男性和女性患者中D等位基因的频率均较高，但仅在男性中达到统计学显著性[男性，第1组：50.8% vs. 第2组：35.0%，p = 0.018，女性，第1组：48.8% vs. 第2组：39.5%，p = 0.231]。本研究虽然受样本量限制，但表明2型糖尿病ESRF患者更频繁地表达DD基因型。这些发现可能证实了之前所指出的韩国2型糖尿病患者中ACE DD基因型与糖尿病肾病进展之间的关系。
