Krajina-Andricević Mirna, Zibar Lada, Glavas-Obrovac- Ljubica, Stefanić Mario, Avdicević Monika, Barbić Jerko
Department of Internal Medicine, General Hospital Vinkovci, Vinkovci, Croatia.
Acta Med Croatica. 2011 Oct;65 Suppl 3:14-9.
The renin-angiotensin system (RAS) has been shown to have important role in blood pressure regulation. Inconsistent results have been reported regarding the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (NCBI ref. SNP ID: rs1799752) and hypertension as well as a contributing factor in the development of diabetic nephropathy. Aim of the study was to investigate the significance of insertion/deletion polymorphism of angiotensin-converting enzyme as contributing factor to blood pressure regulation in type 2 diabetic patients with diabetic nephropathy and those with preserved renal function.
Genomic DNA was extracted from whole blood of 100 patients with diabetic nephropathy and 102 diabetic patients with normal renal function (urinary protein excretion rate less than 300 mg/day and creatinin clearence level > or = 80 ml/min). Blood pressure measurement was done 3 times by a nurse in the supine position, in 15 minutes intervals. Mean arterial pressure (MAP) was calculated according to the standard equation- (systolic pressure + 2 x diastolic pressure)/3, for all measurements. Genotyping was carried out using primers and fluorescent probes in a Lyght Cycler System. Statistical analysis was performed using software package SPSS 16.0 (SPSS inc, Chicago, IL, USA).
Genotype frequencies of the ACE I/D) polymorphysm were in accordance with the Hardy-Weinberg equilibrium. In all subjects, the frequencies of the DD. ID and II genotypes were 0.32; 0.45 and 0.23 respectively. The allelic frequency of the D allele in nephropatby group was 0.82 and 0.72 in the control group. The highest systolic blood pressure was in the subjects with DD genotype. Systolic and mean, arterial pressure were significantly higher in diabetic nephropathy patients compared to patients with preserved kidney function, only if D allele was present (systolic blood pressure: DD t=2,877, p=0,006; ID t=2.733, p=0,008; mean arterial pressure: DD t=2,687, p=0.009; ID t=2,843, p=0,006).
Individuals with type 2 diabetes mellitus who carry the D allele appear to be susceptible to development of the end stage renal disease. D allele might be an additional risk factor for the uncontrolled hypertension in diabetic nephropathy patients.
肾素 - 血管紧张素系统(RAS)已被证明在血压调节中起重要作用。关于血管紧张素转换酶(ACE)插入/缺失(I/D)多态性(NCBI参考SNP ID:rs1799752)与高血压以及糖尿病肾病发生的一个促成因素之间的关联,已有不一致的结果报道。本研究的目的是调查血管紧张素转换酶插入/缺失多态性作为2型糖尿病肾病患者和肾功能正常患者血压调节促成因素的意义。
从100例糖尿病肾病患者和102例肾功能正常的糖尿病患者(尿蛋白排泄率小于300mg/天且肌酐清除率≥80ml/分钟)的全血中提取基因组DNA。护士在仰卧位每隔15分钟测量3次血压。根据标准公式 - (收缩压 + 2×舒张压)/3计算所有测量值的平均动脉压(MAP)。在Light Cycler系统中使用引物和荧光探针进行基因分型。使用软件包SPSS 16.0(美国伊利诺伊州芝加哥市SPSS公司)进行统计分析。
ACE I/D多态性的基因型频率符合哈迪 - 温伯格平衡。在所有受试者中,DD、ID和II基因型的频率分别为0.32、0.45和0.23。肾病组中D等位基因的频率为0.82,对照组为0.72。收缩压最高的是DD基因型的受试者。仅当存在D等位基因时,糖尿病肾病患者的收缩压和平均动脉压显著高于肾功能正常的患者(收缩压:DD t = 2.877,p = 0.006;ID t = 2.733,p = 0.008;平均动脉压:DD t = 2.687,p = 0.009;ID t = 2.843,p = 0.006)。
携带D等位基因的2型糖尿病个体似乎易患终末期肾病。D等位基因可能是糖尿病肾病患者高血压控制不佳的一个额外危险因素。