Angiotensin-II type 1 receptor gene polymorphism and diabetic microangiopathy

Background. Genotypic abnormalities of the renin-angiotensin system have been suggested as risk factors for the development of hypertension, diabetic nephropathy and proliferative retinopathy. Most of the known actions of angiotensin-II are exerted through the angiotensin-II type 1 receptor, which is present particularly in vascular smooth muscle cells, myocardium and the kidney. A transversion of adenine to cytosine at nucleotide position 1166 in the gene coding for the angiotensin-II type 1 receptor has been associated with hypertension in the non-diabetic population. Methods. We studied the relationship between the A(1166)-->C polymorphism in the angiotensin-II type 1 receptor gene in patients with insulin dependent diabetes mellitus (IDDM) and diabetic nephropathy (121 men, 77 women, age 41+/-10 years, diabetes duration 27+/-8 years) and in IDDM patients with normoalbuminuria(116 men, 74 women, age 43+/-10 years, diabetes duration 27+/-8 years). 156 patients (40%) had proliferative retinopathy, 67 patients (17%) had no diabetic retinopathy. Results. There was no difference in genotype distribution between IDDM patients with diabetic nephropathy and normoalbuminuria: 103 (52%) / 81 (41%) / 14 (7%) vs. 97 (51%) / 80 (42%) / 13 (7%) had AA/AC/CC genotypes, respectively. The allele frequencies (A/C) in patients with nephropathy (0.73/0.27) and patients with normoalbuminuria (0.72/0.28) were also similar. No difference in genotype distribution between IDDM patients with proliferative retinopathy and without diabetic retinopathy was found either: 77 (50%) / 66 (42%) / 13 (8%) vs. 42 (63%) / 22 (33%) / 3 (4%) had AA/AC/CC genotypes, respectively. Conclusions. The A(1166)-->C polymorphism in the angiotensin-II type 1 receptor gene does not contribute to the genetic susceptibility to diabetic nephropathy or proliferative retinopathy in Caucasian IDDM patients.