Angiotensin-converting enzyme gene polymorphism as an early predictor of diabetic nephropathy in pediatric type 1 diabetes

Abstract Background Diabetic nephropathy (DN) is a severe complication among type 1 diabetic children, often developing silently before clinical detection. Genetic polymorphisms particularly the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene may influence susceptibility and offer a potential tool for earlier identification. This research aimed to evaluate the role of ACE gene polymorphism as an early predictor of DN among type 1 diabetic children. Methods We included 48 children with type 1 diabetes mellitus in this cross-sectional study. Patients were classified into three groups: without nephropathy (58.3%), with albuminuria and preserved eGFR (27.1%), and with albuminuria and reduced eGFR (14.6%). Clinical evaluation and laboratory investigations including HbA1c, albumin-to-creatinine ratio (ACR), microalbuminuria, serum creatinine, lipid profile, and eGFR were performed. The ACE gene polymorphism was assessed by PCR amplification using allele-specific primers. Results Age showed a significant variation across studied groups ( P = 0.001), with higher values observed among patients with advanced nephropathy. Glycemic control was poorer in affected groups, as indicated by elevated HbA1c levels ( P < 0.001). Renal involvement was evident by increased ACR, microalbuminuria, and serum creatinine, along with a significant decline in eGFR ( P < 0.001). A significant variation in ACE genotype distribution was detected ( P = 0.004), with the DD genotype being more prevalent among patients with DN. Specifically, the D allele was significantly associated with a higher risk of albuminuria (OR = 2.88) and combined renal impairment (OR = 5.28) ( P < 0.001). Furthermore, the DD genotype was linked to worse glycemic and renal parameters ( P < 0.05). Conclusion The ACE gene D allele and DD genotype are significantly associated with early diabetic nephropathy in children with type 1 diabetes mellitus, correlating with reduced eGFR and elevated albuminuria. ACE genotyping can serve as a valuable non-invasive predictive biomarker to identify high-risk pediatric patients for early nephroprotective interventions.