[Angiotensin-converting enyme insertion/deletion polymorphism and blood pressure regulation in type 2 diabetic...

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.