Lack of Association Between the Insertion/Deletion Polymorphism of the Angiotensin-Converting-Enzyme Gene and Diabetic Nephropathy in IDDM Patients

Abstract

The insertion/deletion (I/D) polymorphism of the angiotensin-converting-enzyme (ACE) gene has been reported to be associated with diabetic nephropathy in IDDM. We studied the relationship between this polymorphism and diabetic nephropathy in 210 IDDM patients. Their DNA was analyzed by polymerase chain reaction to type for the presence (I) or absence (D) of the 287 bp fragment in intron 16 of the ACE gene. The relative frequency of the different genotypes was 33.8% (DD), 43.8% (ID), and 22.4% (II). There were no significant differences between the genotypes in age, body-mass-index, blood pressure, plasma total cholesterol and triglycerides. The prevalence of microalbuminuria or nephropathy was 23.9% in the DD, 16.3% in the ID, and 17% in the II genotypes. The higher percentage of microalbuminuria or nephropathy in the DD genotypes was due to an increasing frequency of DD genotypes in the IDDM patients with long diabetes duration. After matching for diabetic retinopathy, gender, and diabetes duration, there was no association between the ACEI/D polymorphism and diabetic nephropathy. In conclusion, these results suggest that the ACE DD genotype cannot be regarded as a risk factor for diabetic nephropathy, but may even be associated with diabetes duration and thus longevity in IDDM patients.

MTHFR C677T, A1298C and ACE I/D polymorphisms as risk factors for diabetic nephropathy among type 2 diabetic patients

“…Similarly MTHFR A1298C polymorphism was reported to be negatively associated with DN in the studies done among Jewish50 and Polish 48 cases. Similarly, lack of an association between kidney function and ACE (DD/II) was reported in previous studies done among Chinese,51 German,52,53 Danish,54 Turkish,4,55,56 Korean, 57 Iranian 58,59 and Dutch 60 diabetic cases.…”

Association of angiotensin‐converting enzyme DD genotype with 24‐h blood pressure abnormalities in normoalbuminuric children and adolescents with Type 1 diabetes

“…The implication of ACE genotype in the pathogenesis of nephropathy in Type 1 diabetes is controversial. Many studies showed an association [6][7][8][9][10][11][12][13][14] but others were not able to provide evidence [15][16][17][18][19][20]. On the basis of meta-analyses, more data support the concept that rather the progression than the development of nephropathy is influenced by ACE genotypes [45,46], however, an effect on the development of microalbuminuria can not be entirely excluded [47].…”

“…Several clinical studies have found that the D allele is associated with an increased risk of diabetic nephropathy [6][7][8][9][10][11][12] which have been supported by morphological findings [13,14]. However, other studies have failed to demonstrate any relationship between the ACE genotype and diabetic kidney damage [15][16][17][18][19][20].…”

Combination of Angiotensin Converting Enzyme Insertion/Deletion (I/D) (rs4646994) and VEGF Polymorphism (+405G/C; rs2010963) Synergistically Associated With the Development, of Albuminuria in Iranian Patients With Type 2 Diabetes

“…In the present study, we had the advantage of a close match between the two groups of patients in a long list of potentially confounding variables. It should be noted, however, that there are several reports on type 1 diabetes without statistically significant results ( 29 , 37 ).…”