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.
Seki
N
N
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hashimoto
N
N
Suzuki
Y
Y
Yagui
K
K
Saito
Y
Y
D000368:Aged; D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000097:blood
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D044139:Receptor, Angiotensin, Type 2; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A