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.
Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: a methodologic appraisal and systematic review.
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).
ACE gene polymorphism was analyzed by polymerase chain reaction in 460 individuals consisting of 174 cases of DN, 175 cases of Type 2 diabetes mellitus (DM), and 111 controls.
Although we acknowledge certain problems in the design of the study the results in this large cohort suggest that the I/D polymorphism of the ACE gene does not play a major role in the development of DN.
The results of this study are evidence that the risk of diabetic nephropathy in IDDM is influenced by genetic variability at the ACE locus, but the responsible variant is not the I/D polymorphism in intron 16.
In conclusion, these results suggest that the ACE locus may be associated with longevity and survival in patients with type I diabetes rather than diabetic nephropathy or microvascular disease per se.
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.
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.
We analyzed clinical parameters and ACE genotype distribution between type 2 diabetic patients at the extremes of renal risk, i.e. an end-stage renal failure (ESRF) group (n = 103, group 1) who were on dialysis therapy due to progression of diabetic nephropathy, and a no progression group (n = 88, group 2) who had maintained normal renal function and normoalbuminuria for more than 15 years.
Is the presence of retinopathy of practical value in defining cases of diabetic nephropathy in genetic association studies? The experience with the ACE insertion/deletion polymorphism in 53 studies comprising 17,791 subjects.
Our independent case-control study provides no evidence that common variants in ACE, ACE2 and AGTR1 play a major role in genetic susceptibility to diabetic nephropathy in a white population with Type1 diabetes.
Although the ACE gene polymorphism's potential link to diabetic nephropathy in patients with type 1 diabetes has been debated, the most definitive studies show that an association exists.
Allelic frequencies of the ACE-D and AGT-235T alleles were similar between patients with and without nephropathy in either type of diabetes, and accordingly, there was no significant association between diabetic nephropathy and the ACE or AGT genotype.
Using multivariate logistic regression analyses, we investigated the independent or synergistic effects of the ACE I/D and PAI-1 4G/5G polymorphisms on the development of diabetic nephropathy and macroangiopathy in 208 patients with non-insulin dependent diabetes mellitus (NIDDM) over a 15 year period.
A cross-sectional study was conducted to examine the relationship between glomerular hyperfiltration and ACE (I/D) polymorphism in 76 type 1 diabetic children and adolescents without diabetic nephropathy (mean +/- SD: age 16 +/- 3 years; diabetes duration 7 +/- 4 years; age at diabetes onset 9 +/- 4 years; HbA1c 9.5 +/- 1.9%).
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.
These results suggest that: (1) the ACE gene I/D polymorphism influences glomerular filtration and renal plasma flow rates in patients with early uncomplicated IDDM; and (2) differences in renal hemodynamic function do not appear to explain the protection against the development of diabetic nephropathy offered by the I allele.
The present study investigated the influence of insertion (I)/deletion (D) polymorphism of the angiotensin II-converting enzyme (ACE) gene in combination with endothelial nitric oxide (eNOS) G894T polymorphism on the predisposition to diabetic nephropathy (DN).
Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients.