Genetic polymorphisms of the renin-angiotensin system and complications ofinsulin-dependent diabetes mellitus

Objective, Patients with insulin-dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascula r diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among popula tions. Methods. In 257 Dutch IDDM patients (188 with urinary albumin excretion (UA E) <30 mg/24 h), logistic regression analysis was used to study the relatio nships among, on the one hand, the insertion/deletion gene polymorphism of the angiotensin-converting enzyme gene (ACE-ID), the M235T gene polymorphis m of the angiotensinogen gene (AGT-M235T), and the A1166C gene polymorphism of the angiotensin type 1 receptor gene (AT1-A1166C), and, on the other ha nd, UAE, retinopathy, hypertension, and coronary heart disease. Results. The T-allele of the AGT-M235T polymorphism was associated with an increased risk of an elevated UAE (odds ratio (OR) 3.03; 95% confidence int erval (CI) 1.06-8.61), but only when interaction with the D-allele of the A CE-ID polymorphism was considered. A previously described positive interact ion between the T-allele of the AGT-M235T polymorphism and the D-allele of the ACE-ID polymorphism could not be confirmed. The T-allele was also assoc iated with an increased risk of retinopathy (OR 3.89, 95% CI 1.79-8.47). Th e CC-genotype of the AT1-A1166C polymorphism was associated with hypertensi on (OR 3.58; 95% CI 1.23-10.37). Conclusions, In a Dutch IDDM population, including 69 patients with (incipi ent) diabetic nephropathy, the T-allele of the AGT-M235T polymorphism is as sociated with an elevated UAE and diabetic retinopathy and the CC-genotype of the AT1-A1166C polymorphism is associated with hypertension. A previousl y described interaction between the AGT-M235T and the ACE-ID polymorphisms could not be confirmed. Since the number of nephropathic patients in this s tudy is small, these conclusions must be interpreted with caution.