Relationship between polymorphisms in the renin-angiotensin system and nephropathy in type 2 diabetic patients

Renin Angiotensin system is involved in renal function and its polymorphisms may influence diabetic nephropathy. ID ACE polymorphism modulates ACE level whereas M235T AGT polymorphism is involved in arterial hypertension. The A1166C AT1R polymorphism is involved in arterial hypertension and in diabetic retinopathy.

Two hundred thirty five type 2 diabetic patients were enrolled in this transversal study. Data were documented for clinical characteristics of the population, HbA(1c), urinary albumin excretion, presence of retinopathy or antihypertensive treatment. Polymorphisms were analyzed by PCR techniques. The patients were divided into 3 groups: group 1, without nephropathy (n=118), group 2, microalbuminuria (n=78), group 3, macroalbuminuria (n=39).

Diabetes duration was longer (p<0.001), retinopathy (p<0.001) and antihypertensive treatment (p<0.02) were more frequent in group 3 compared to group 1 and 2. The I/D ACE and M235T AGT polymorphisms were not differently distributed between the three groups. In contrast, the CC genotype of the AT1R polymorphism was overrepresented in group 2 (p=0.021). The presence of the CC AT1R genotype considerably increased the incidence of albuminuria after 10 years of diabetes (AA vs CC p=0.01), particurlarly in men. No effect was seen with I/D ACE and M235T AGT polymorphisms.

In conclusion, we observed an interaction of A1166C AT1R polymorphism with diabetes in men but not of I/D ACE and M235T AGT polymorphisms.