Differential effects of RAS inhibitors associated with ACE gene polymorphisms in type 2 diabetic nephropathy.

Blood pressure and genetic factors are important factors for diabetic nephropathy. We investigated the relationship between the efficacy of renin angiotensin system (RAS) inhibitors and angiotensin-converting enzyme (ACE) genotypes. Patients with type 2 diabetes without proteinuria, were treated with RAS inhibitors, the first being an ACE inhibitor (ACEI) and the second, an angiotensin II (ATII) receptor blocker (ARB) for 8 weeks each. There was no significant difference (except serum ACE activity) between the two treatments. However, by analysis segregated with ACE gene polymorphism, ARB significantly decreased transforming growth factor-beta1 (TGF-beta) compared to ACEI in patients with the I/I genotype but not in patients with the D/I+D/D genotype. DeltaATII and DeltaTGF-beta have a negative correlation with the I/I genotype and a positive correlation with the D/I+D/D genotypes. These correlation coefficients are significantly different. We suggest that in I/I patients, TGF-beta was reduced by ARB via effects on (ATII) type 2 receptors (AT2). In our experiments, the effect of ARB on TGF-beta reduction was only detected by segregation of ACE genotypes. This indicates that the selection of medicine in light of a patient's genotype is important in treating diabetic nephropathy.