We have examined the association of four candidate genes, angiotensin converting enzyme (ACE): insertion/deletion (I/D) polymorphism, plasminogen activator inhibitor-1 (PAI-1): 4G/5G polymorphism, decorin: 179/183/185 polymorphism and Werner syndrome helicase: C/R polymorphism, with the presence of diabetic nephropathy in Type 1 diabetic patients.
ACE and AGT gene polymorphisms may not play a role in the protective or accelerative effect against the development of diabetic nephropathy in the patients with or without proliferative retinopathy, but ACE gene polymorphism might be related to an arteriosclerotic family history in Japanese IDDM patients.
Diabetic patients with coexistence of PAI-1 4G/4G genotype and ACE D alleles had a higher incidence of diabetic nephropathy (22 vs. 7%, P = 0.012) than those with other combinations of genotypes.
The D allele of the angiotensin-converting enzyme (ACE) gene has been linked with diabetic nephropathy and IgA glomerulonephritis and with faster renal disease progression.
Influence of insertion/deletion polymorphism in the ACE-I gene on the progression of diabetic glomerulopathy in type 1 diabetic patients with microalbuminuria.
The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05).
Therefore, we investigated the interaction between long-term glycaemic control and three polymorphisms in the genes coding for AGTR1 (A1166-->C), angiotensin converting enzyme (ACE/ID) and angiotensinogen (M235T) on risk of developing diabetic nephropathy.
A substitution (M235T) polymorphism in angiotensinogen (AGT) may interact with ACE I/D polymorphism for the risk of diabetic nephropathy, but their prognostic values have to be established by follow-up studies.
Until recently, pharmacologic intervention in the RAS has focused on the ACE step, with documented success being reported in the prevention of diabetic nephropathy and ESRD using ACE inhibitors.
The frequencies of ACE-DD genotype and ACE-D allele were much higher in DN(+) group than in DN (-) group (0.25 vs 0.05, 0.47 vs 0.29, respectively), so were the frequencies of TT genotype and T allele in AGT-M235T (0.73 vs 0.54, 0.85 vs 0.68, respectively).
Because ACE insertion/deletion (I/D) polymorphism has been shown to be associated with diabetes, hypertension, coronary artery diseases, and diabetic nephropathy, and because plasma ACE concentration has been found to be associated with plasma triglyceride and total cholesterol levels in patients with type 2 diabetes, the goal of this study was to investigate whether ACE gene I/D polymorphism is associated with metabolic syndrome in Chinese subjects with type 2 diabetes.
Since 1992, the angiotensin I-converting enzyme (ACE) deletion/deletion (D/D) genotype has been linked to several cardiovascular diseases, including diabetic nephropathy.
We investigated the expression of nephrin in human kidney tissue from patients with diabetic nephropathy to elucidate its relationship with proteinuria and the effects of anti-proteinuric therapy with angiotensin converting enzyme inhibition.
We used this method to analyze a) a highly polymorphic pentanucleotide repeat (CCTTT)(n) locus within the 5'-putative promoter region of the human inducible nitric oxide synthase gene (iNOS5) which is associated with diabetic complications and infectious diseases; b) a bi-allelic 27 bp VNTR region within intron 4 of endothelial nitric oxide gene (eNOS27) which is associated with hypertension in type 2 diabetes patients with coronary heart disease and excess risk of advanced diabetic nephropathy in type 1 diabetes patients and c) an insertion/deletion polymorphism within the gene encoding angiotensin-converting enzyme (ACE/ID) which is associated with cardiovascular pathology and nitric oxide activity, and is in strong linkage disequilibrium with functional variants.
Multivariate logistic regression analysis [hypertension, gender, age, duration of diabetes, hemoglobin (HbA1c), usage of angiotensin-converting enzyme (ACE) inhibitor, and cholesterol level] showed that TGF-beta genotype (P = 0.03) is an independent predictor for type 2 DMN.
The two main treatment strategies for prevention of diabetic nephropathy are improved glycaemic control and blood pressure lowering, particularly using drugs such angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists.