Background: Diabetic nephropathy is a major cause of morbidity and mortality among young adults with type 1 diabetes mellitus. Strong evidence exists in multiple studies for genetic predisposition of diabetic nephropathy. Genetic studies have revealed that the genes for the reninangiotensin system (RAS) are highly polymorphic, one of such is insertion/deletion polymorphism in ACE gene. This polymorphism was associated with the circulating ACE level and increased plasma activity of this enzyme.
Objective and hypotheses: The aim of the present study was to determine the relationship between ACE gene insertion/deletion polymorphisms, serum ACE activity and the risk of diabetic nephropathy in patients with type 1 diabetes mellitus.
Method: The current study included thirty type 1 diabetic patients with diabetic nephropathy. Their mean age was 14.73±4.17 years and their mean duration of diabetes was 8.47±3.43 years. Also thirty type 1 diabetic patients with no evidence of nephropathy were included as a control group. Their mean age was 13.57±3.72 years and their mean duration of diabetes was 8.80±3.47 years. ACE DD/ID/II genotypes were determined by PCR, and the quantity of serum ACE was determined using ELISA.
Results: The current study revealed that ACE enzyme activity was significantly higher in diabetic patients with nephropathy (mean 74.2 vs 53.3 ng/ml, P=0.04). Diabetics with microalbuminuria had higher frequency of DD and ID alleles (13 and 63 vs 10 and 46% respectively), also they had lower frequency of II allele (23.3 vs 43.3%) with a borderline statistical significance (P=0.05). The overall allelic occurrence of deletion (D) was insignificantly higher in those with nephropathy (45 vs 33%, P=0.095).
Conclusion: ACE enzyme activity and ACE genotypes (DD and ID) are higher in type 1 diabetic children with microalbuminuria. Genetic susceptibility might have a role in diabetic nephropathy.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology